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Showing papers in "Combinatorial Chemistry & High Throughput Screening in 2020"


Journal ArticleDOI
TL;DR: Among recently reported heterogeneous catalytic systems, Fe3O4/P4VP-Pd is recommended due to its high catalytic performance, convenience of the preparation process, excellent biocompatibility, economic benefits, and well reusability.
Abstract: OBJECTIVE Herein, a novel heterogeneous catalytic system constructed of iron oxide and palladium nanoparticles is presented. Firstly, a convenient synthetic pathway for the preparation of this catalytic system is introduced, then the application of the fabricated nanocomposite in the Pd-catalyzed C─C coupling reactions is monitored. High reaction yields (98%) have been obtained in short reaction time, by using this catalytic system. MATERIALS AND METHODS Fe3O4/P4VP-Pd catalytic system was fabricated via an in situ method by 4- vinylpyridine (4-VP). In this regard, all the essential structural analyses such as FT-IR, EDX, VSM, and TGA have been performed on the Fe3O4/P4VP-Pd catalytic system to investigate its properties. The spherical morphology of the NPs and their uniform size have also been studied by the SEM method. Further, the reaction progress was controlled by thin-layer chromatography. Finally, NMR analysis was used to identify the synthesized biphenyl pharmaceutical derivatives. RESULTS High efficiency of this catalytic system has been precisely investigated and the optimal conditions were determined. The catalytic process is carried out in 20 min, under mild conditions (room temperature). Then, the purification process is easily performed via magnetic separation of the catalyst NPs. After completion of the synthesis reaction, the NPs were collected, washed, and reused several times. CONCLUSION Among recently reported heterogeneous catalytic systems, Fe3O4/P4VP-Pd is recommended due to its high catalytic performance, convenience of the preparation process, excellent biocompatibility, economic benefits, and well reusability. Overall, in order to save time in the complex synthetic processes and also prevent using so many chemical reagents and solvents for the purification process, the presented catalytic system could be suitable for scaling up and applying for the industrial applications.

32 citations


Journal ArticleDOI
TL;DR: The network model with multiple networks was superior to that with certain single network and classic model, indicating the superiority of the proposed model.
Abstract: Background Identification of drug-target interaction is essential in drug discovery. It is beneficial to predict unexpected therapeutic or adverse side effects of drugs. To date, several computational methods have been proposed to predict drug-target interactions because they are prompt and low-cost compared with traditional wet experiments. Methods In this study, we investigated this problem in a different way. According to KEGG, drugs were classified into several groups based on their target proteins. A multi-label classification model was presented to assign drugs into correct target groups. To make full use of the known drug properties, five networks were constructed, each of which represented drug associations in one property. A powerful network embedding method, Mashup, was adopted to extract drug features from above-mentioned networks, based on which several machine learning algorithms, including RAndom k-labELsets (RAKEL) algorithm, Label Powerset (LP) algorithm and Support Vector Machine (SVM), were used to build the classification model. Results and conclusion Tenfold cross-validation yielded the accuracy of 0.839, exact match of 0.816 and hamming loss of 0.037, indicating good performance of the model. The contribution of each network was also analyzed. Furthermore, the network model with multiple networks was found to be superior to the one with a single network and classic model, indicating the superiority of the proposed model.

28 citations


Journal ArticleDOI
TL;DR: The major contribution of this article is that, due to the complexity of computing the exact partition dimension, it is shown that all the graphs discussed in results have partition dimension either less or equals to 4, but it cannot been be greater than 4.
Abstract: AIMS AND OBJECTIVE The idea of partition and resolving sets plays an important role in various areas of engineering, chemistry and computer science such as robot navigation, facility location, pharmaceutical chemistry, combinatorial optimization, networking, and mastermind game. METHOD In a graph to obtain the exact location of a required vertex which is unique from all the vertices, several vertices are selected this is called resolving set and its generalization is called resolving partition, where selected vertices are in the form of subsets. Minimum number of partitions of the vertices into sets is called partition dimension. RESULTS It was proved that determining the partition dimension a graph is nondeterministic polynomial time (NP) problem. In this article, we find the partition dimension of convex polytopes and provide their bounds. CONCLUSION The major contribution of this article is that, due to the complexity of computing the exact partition dimension we provides the bounds and show that all the graphs discussed in results have partition dimension either less or equals to 4, but it cannot been be greater than 4.

25 citations


Journal ArticleDOI
TL;DR: This document stores the name of the company and a description of its products and staff, as well as a brief description of the products and procedures used to produce them.
Abstract:

23 citations


Journal ArticleDOI
TL;DR: ZIKVPred-PseAAC can help in predicting the ZIKV proteins in an efficient and accurate way and can provide baseline data for the discovery of new drugs and biomarkers against ZikV.
Abstract: BACKGROUND ZIKV has been a well-known global threat, which hits almost all of the American countries and posed a serious threat to the entire globe in 2016. The first outbreak of ZIKV was reported in 2007 in the Pacific area, followed by another severe outbreak, which occurred in 2013/2014 and subsequently, ZIKV spread to all other Pacific islands. A broad spectrum of ZIKV associated neurological malformations in neonates and adults has driven this deadly virus into the limelight. Though tremendous efforts have been focused on understanding the molecular basis of ZIKV, the viral proteins of ZIKV have still not been studied extensively. OBJECTIVES Herein, we report the first and the novel predictor for the identification of ZIKV proteins. METHODS We have employed Chou's pseudo amino acid composition (PseAAC), statistical moments and various position-based features. RESULTS The predictor is validated through 10-fold cross-validation and Jackknife testing. In 10- fold cross-validation, 94.09% accuracy, 93.48% specificity, 94.20% sensitivity and 0.80 MCC were achieved while in Jackknife testing, 96.62% accuracy, 94.57% specificity, 97.00% sensitivity and 0.88 MCC were achieved. CONCLUSION Thus, ZIKVPred-PseAAC can help in predicting the ZIKV proteins efficiently and accurately and can provide baseline data for the discovery of new drugs and biomarkers against ZIKV.

22 citations


Journal ArticleDOI
TL;DR: Osimertinib analouge 48, 50, 60, 61, 67, 75, 80, 86, 89, 92, 93, 116 and 124 were the most active and selective compounds against T790M EGFR mutants compared to Osimert inib.
Abstract: Background Lung cancer has become the prominent cause of the cancer-related deaths globally. More than 80 % of all lung cancers have been diagnosed with Non- Small Cell Lung Cancer (NSCLC). The USFDA approved osimertinib to treat patients with metastatic T790M EGFR NSCLC on a regular basis in March 2017. Recently, C797S mutation to osimertinib has been reported, which indicates the need for structural modification to overcome the problem of mutation. Objective In this bioinformatics study, we have evaluated the impact of various acrylamide as an electrophilic warhead on the activity and selectivity of osimertinib. Result Osimertinib analouge 48, 50, 60, 61, 67, 75, 80, 86, 89, 92, 93, 116 and 124 were the most active and selective compounds against T790M EGFR mutants compared to Osimertinib. Conclusion These compounds also showed less inclination towards WT-EGFR.

21 citations


Journal ArticleDOI
TL;DR: The results showed molecular docking combined with network pharmacology is a feasible strategy for exploring bioactive compounds and mechanisms of Chinese medicines, and Guizhi-Shaoyao-Zhimu decoction treat diabetes through multi-components and multi-targets & pathways.
Abstract: Aim and objective This study was designed to explore the active compounds and significant pathways of Guizhi-Shaoyao-Zhimu decoction (GSZD) for treating diabetes mellitus using molecular docking combined with network pharmacology. Materials and methods Chemical constituents of GSZD and diabetes-related target proteins were collected from various databases. Then, compounds were filtered by Lipinski's and Veber's rules with Discovery studio software. The "Libdock" module was used to carry out molecular docking, and LibDockScores, default cutoff values for hydrogen bonds, and van der Waals interactions were recorded. LibDockScore of the target protein and its prototype ligand was considered as the threshold, and compounds with higher LibDockScores than the threshold were regarded as the active constituents of GSZD. Cytoscape software was used to construct the herb-active molecule-target interaction network of GSZD. ClueGO and CluePedia were applied to enrich the analysis of the biological functions and pathways of GSZD. Results A total of 275 potential active compounds with 57 possible pathways in GSZD were identified by molecular docking combined with network pharmacology. TEN, INSR, PRKAA2, and GSK3B are the four most important target proteins. Gancaonin E, 3'-(γ,γ-dimethylallyl)-kievitone, aurantiamide, curcumin and 14-O-cinnamoylneoline, could interact with more than 14 of the selected target proteins. Besides, 57 potential pathways of GSZD were identified, such as insulin signaling pathway, metabolites and energy regulation, glucose metabolic process regulation, and positive regulation of carbohydrate metabolic process, etc. Conclusion: These results showed that molecular docking combined with network pharmacology is a feasible strategy for exploring bioactive compounds and mechanisms of Chinese medicines, and GSZD can be used to effectively treat diabetes through multi-components and multi-targets & pathways.

21 citations


Journal ArticleDOI
TL;DR: The synthesized hydrazones 3a, 3b, 3f and 3g were found to be most active compounds and showed MIC values of 12.5 μg/mL, which would definitely help the medicinal chemists to develop potent analogues containing hydrazine motifs in them.
Abstract: Background Since the last few decades, the healthcare sector is facing the problem of the development of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) infections all over the world. Regardless of the current healthcare progress for the treatment of mycobacterial infections, we are still unable to control addition of every year 9 million new cases of tuberculosis (TB). Objective We had an objective to synthesize some novel hydrazones, which were further subjected to characterization, Photoluminescence study, in vitro anti-mycobacterium testing and in silico ADMET predictions. Methods Some new hydrazone derivatives have been successfully prepared by the condensation reaction in the present study. All the compounds were characterized by using FTIR, NMR, UV, Fluorescence spectroscopic techniques. Results All our newly synthesized compounds showed strong electronic excitation at 292.6 - 319.0 nm and displayed more intense emissions in the 348 - 365 nm regions except compound 3i. The newly synthesized hydrazones 3a, 3b, 3f and 3g were found to be the most active compounds and showed MIC (Minimum inhibitory concentrations) values of 12.5 μg/mL. Conclusion In the realm of development of more potent, effective, safer and less toxic antituberculosis agents; our current study would definitely help the medicinal chemists to develop potent analogues containing hydrazine motifs in them.

17 citations


Journal ArticleDOI
TL;DR: This study shows that the anti-fatigue effect of PR has multi-component, multi-target and multi-pathway.
Abstract: Background and objective A large number of people are facing the danger of fatigue due to the fast-paced lifestyle. Fatigue is common in some diseases, such as cancer. The mechanism of fatigue is not definite. Traditional Chinese medicine is often used for fatigue, but the potential mechanism of Polygonati Rhizoma (PR) is still not clear. This study attempts to explore the potential anti-fatigue mechanism of Polygonati Rhizoma through virtual screening based on network pharmacology. Methods The candidate compounds of PR and the known targets of fatigue are obtained from multiple professional databases. PharmMapper Server is designed to identify potential targets for the candidate compounds. We developed a Herbal medicine-Compound-Disease-Target network and analyzed the interactions. Protein-protein interaction network is developed through the Cytoscape software and analyzed by topological methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment are carried out by DAVID Database. Finally, we develop Compound-Target-Pathway network to illustrate the anti-fatigue mechanism of PR. Results This approach identified 12 active compounds and 156 candidate targets of PR. The top 10 annotation terms for GO and KEGG were obtained by enrichment analysis with 35 key targets. The interaction between E2F1 and PI3K-AKT plays a vital role in the anti-fatigue effect of PR due to this study. Conclusion This study demonstrates that PR has multi-component, multi-target and multipathway effects.

14 citations


Journal ArticleDOI
TL;DR: Close expressions of several distance-based topological indices of three-layered single-walled titania nanosheet TNS_3 [m,n] molecular graph are obtained for the cases m≥ n and m < n.
Abstract: AIM AND OBJECTIVE Nanostructures are objects whose sizes are between microscopic and molecular. The most significant of these new elements are carbon nanotubes. These elements have extraordinary microelectronic properties and many other exclusive physiognomies. Recently, researchers have given the attention to the mathematical properties of these materials. The aim and objective of this research article is to investigate the most important molecular descriptors namely Wiener, edge-Wiener, vertex-edge-Wiener, vertex-Szeged, edge-Szeged, edge-vertex-Szeged, total-Szeged, PI, Schultz, Gutman, Mostar, edge-Mostar, and total-Mostar indices of three-layered single-walled titania nanosheets. By computing these topological indices, materials science researchers can have a better understanding of structural and physical properties of titania nanosheets, and thereby more easily synthesizing new variants of titania nanosheets with more amenable physicochemical properties. METHODS The cut method turned out to be extremely handy when dealing with distance-based graph invariants which are in turn among the central concepts of chemical graph theory. In this method, we use the Djokovic -Winkler relation to find the suitable edge cuts to leave the graph into exactly two components. Based on the graph theoretical measures of the components, we obtain the desired topological indices by mathematical computations. RESULTS In this paper, distance-based indices for three-layered single-walled titania nanosheets were investigated and given the exact expressions for various dimensions of three-layered single-walled titania nanosheets. These indices may be useful in synthesizing new variants of titania nanosheets and the computed topological indices play an important role in studies of Quantitative structure-activity relationship (QSAR) and Quantitative structure-property relationship (QSPR). CONCLUSION In this paper, we have obtained the closed expressions of several distance-based topological indices of three-layered single-walled titania nanosheet TNS_3 [m,n] molecular graph for the cases m≥ n and m < n. The graphical validations for the computed indices are done and we observe that the Wiener types, Schultz and Gutman indices perform in a similar way whereas PI and Mostar type indices perform in the same way.

13 citations


Journal ArticleDOI
TL;DR: The current perspective described the recent updates of chalcone moiety linked with the pharmacophores of flurbiprofen and rivastigmine hybrids as selective ChE/MAO-B inhibitors for the prophylactic agents for AD.
Abstract: Multi-functional design of ligands emerged as a new drug design paradigm of Alzheimer's disease (AD). Given the complexity of AD, the molecules showing dual inhibition of monoamine oxidase (MAO) and acetylcholinesterase (AChE) with neuroprotective properties could prevent the progressive neural degeneration effectively. Numerous studies documented that chalcone is a privileged structural framework for the inhibition of both MAO and AChE. The recent studies suggested that the development of chalcone candidates endowed with pharmacophores of FDA approved drugs may become an active molecules in the field of current AD research. The current perspective described the recent updates of chalcone moiety linked with the pharmacophores of flurbiprofen and rivastigmine hybrids as selective ChE/MAO-B inhibitors for the prophylactic agents for AD.

Journal ArticleDOI
TL;DR: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury and is found to be significantly improved in the IRI + ASX group.
Abstract: BACKGROUND Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. OBJECTIVE The aim of this study was to investigate the role of ASX on brain IRI. METHODS A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. RESULTS In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). CONCLUSION Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

Journal ArticleDOI
TL;DR: NPs have a potential anticancer properties against human lung adenocarcinoma cells and may induce cell death effectively and be a potent modality to treat this type of cancer.
Abstract: AIMS To prepare lamivudine (LAM)-loaded-nanoparticles (NPs) that can be used in lung cancer treatment. To change the antiviral indication of LAM to anticancer. BACKGROUND The development of anticancer drugs is a difficult process. One approach to accelerate the availability of drugs is to reclassify drugs approved for other conditions as anticancer. The most common route of administration of anticancer drugs is intravenous injection. Oral administration of anticancer drugs may considerably change current treatment modalities of chemotherapy and improve the life quality of cancer patients. There is also a potentially significant economic advantage. OBJECTIVE To characterize the LAM-loaded-NPs and examine the anticancer activity. METHODS LAM-loaded-NPs were prepared using Nano Spray-Dryer. Properties of NPs were elucidated by particle size (PS), polydispersity index (PDI), zeta potential (ZP), SEM, encapsulation efficiency (EE%), dissolution, release kinetics, DSC and FT-IR. Then, the anticancer activity of all NPs was examined. RESULTS The PS values of the LAM-loaded-NPs were between 373 and 486 nm. All NPs prepared have spherical structure and positive ZP. EE% was in a range of 61-79%. NPs showed prolonged release and the release kinetics fitted to the Weibull model. NPs structures were clarified by DSC and FT-IR analysis. The results showed that the properties of NPs were directly related to the drug:polymer ratio of feed solution. NPs have potential anticancer properties against A549 cell line at low concentrations and non-toxic to CCD 19-Lu cell line. CONCLUSION NPs have potential anticancer properties against human lung adenocarcinoma cells and may induce cell death effectively and be a potent modality to treat this type of cancer. These experiments also indicate that our formulations are non-toxic to normal cells. It is clear that this study would bring a new perspective to cancer therapy.

Journal ArticleDOI
TL;DR: The results suggest that the phosphorylation of these three serine residues weakens the binding of GS-CA1 with CA and casts derogatory effect on inhibition potential of this inhibitor, but it supports the stability of HIV-1 CA structure that can enhance regulation and replication of AIDS-1 in host cells.
Abstract: BACKGROUND Human Immunodeficiency Virus 1 (HIV-1) is a lentivirus, which causes various HIV-associated infections. The HIV-1 core dissociation is essential for viral cDNA synthesis and phosphorylation of HIV-1 capsid protein (HIV-1 CA) plays an important role in it. OBJECTIVE The aim of this study was to explicate the role of three phosphoserine sites i.e. Ser109, Ser149 and Ser178 in the structural stability of HIV-1 CA, and it's binding with GS-CA1, a novel potent inhibitor. METHODS Eight complexes were analyzed and Molecular Dynamics (MD) simulations were performed to observe the stability of HIV-1 CA in the presence and absence of phosphorylation of serine residues at four different temperatures i.e. 300K, 325K, 340K and 350K, along with molecular docking and DFT analysis. RESULTS The structures showed maximum stability in the presence of phosphorylated serine residue. However, GS-CA1 docked most strongly with the native structure of HIV-1 CA i.e. binding affinity was -8.5 kcal/mol (Ki = 0.579 µM). CONCLUSION These results suggest that the phosphorylation of these three serine residues weakens the binding of GS-CA1 with CA and casts derogatory effect on inhibition potential of this inhibitor, but it supports the stability of HIV-1 CA structure that can enhance regulation and replication of HIV-1 in host cells.

Journal ArticleDOI
TL;DR: Lignans and Neolignans may be an alternative for the treatment of Tuberculosis through QSAR, Molecular Modeling and ADMET studies and most molecules did not show any toxicity according to the evaluated parameters.
Abstract: Background Tuberculosis is a disease with high incidence and high mortality rate, especially in Brazil. Although there are several medications available for treatment, in cases of resistance, there is a need to use more than one medication. Objective Therefore, cases of toxicity increase and reports of resistance have been worrying the population. In addition, some medications have a short period of effectiveness. To achieve the goal, ligand-based and structure-based approaches were used. Methods Thus, in an attempt to discover potent inhibitors against Mycobacterium tuberculosis enzymes, we sought to identify natural products with high therapeutic potential for the treatment of Tuberculosis through QSAR, Molecular Modeling and ADMET studies. Results The results showed that the models generated from two sets of molecules with known activity against M. tuberculosis enzymes InhA and PS were able to select 11 and 8 compounds, respectively, between Lignans and Neolignans with 50 to 60% activity probability. In addition, molecular docking contributed to confirm the mechanism of action of compounds and increase the accuracy of methodologies. All molecules showed higher binding energy values for the drug Isoniazid. We conclude that compounds 33, 34, 110, 114 and 133 are promising for InhA target and compounds 07, 08, 19, 21, 42, 48, 75 and 141 for target PS. In addition, most molecules did not show any toxicity according to the evaluated parameters. Conclusion Therefore, Lignans and Neolignans may be an alternative for the treatment of Tuberculosis.

Journal ArticleDOI
Sizhen Gu1, Yan Xue1, Yuli Zhang1, Kanjun Chen1, Shigui Xue1, Ji Pan1, Yini Tang1, Hui Zhu1, Huan Wu1, Danbo Dou1 
TL;DR: The results screened by GO and KEGG enrichment analysis showed that FSEC played a comprehensive therapeutic role in immune recognition, anti-inflammation and antioxidation mainly through IL-17, TNF, Toll-like receptor, NF-kappa B, and Th17 cell differentiation.
Abstract: Aim and objective Five-Flavor Sophora flavescens Enteric-Coated Capsules (FSEC) are the only proprietary Chinese medicine approved for the treatment of ulcerative colitis (UC) in China. Phase II and III clinical trials have shown that the curative effect of FSEC in relieving UC was not inferior to that of mesalazine granules and enteric-coated tablets, but its pharmacological mechanism is unclear. Therefore, the network pharmacology is used to reveal the more comprehensive effective components and targets of FSEC in the treatment of UC. Methods We screened the components of FSEC based on the TCMSP database, determined the action targets of these compounds through target fishing, and integrated the UC disease targets of several disease gene databases. The FSEC-UC composite targets were obtained by matching the two results, and then a PPI network was constructed to analyze the relationship between these targets, and the core targets were selected by topological correlation parameters. Finally, GO-BP and KEGG enrichment analyses were carried out using the clusterProfiler software package. Results One hundred and sixty active components of FSEC were identified and 77 targets were obtained. Of these, 30 core targets were the main targets of FESC in the treatment of UC. And quercetin, kaempferol, luteolin and mangiferin were regarded as the core active components of FSEC. The results screened by GO and KEGG enrichment analysis showed that FSEC played a comprehensive therapeutic role in immune recognition, anti-inflammation and antioxidation mainly through IL-17, TNF, Toll-like receptor, NF-kappa B, and Th17 cell differentiation. Conclusion The molecular mechanism of UC remission induced by FSEC was predicted by network pharmacology. These findings provide an important theoretical basis for further study of the effective substances and mechanism of FSEC in the treatment of UC.

Journal ArticleDOI
TL;DR: Consumption of flaxseed in different forms has valuable effect and protects against cardiovascular disease, hypertension, diabetes, dyslipidemia, inflammation and some other complications.
Abstract: Background Flaxseed (Linum usitatissimum) is an oil-based seed that contains high amounts of alpha-linolenic acid, linoleic acid, lignans, fiber and many other bioactive components which is suggested for a healthier life. Nowadays, flaxseed is known as a remarkable functional food with different health benefits for humans and protects against cardiovascular disease, diabetes, dyslipidemia, obesity and altogether metabolic syndrome. Methods To review the bioactive components of flaxseed and their potential health effects, PubMed and Scopus were searched from commencement to July 2019. Keywords including: "flaxseed", "Linum usitatissimum", "metabolic syndrome", "obesity", "inflammation", "insulin resistance", "diabetes", "hyperlipidemia" and "menopause" were searched in the databases with varying combinations. Conclusion Consumption of flaxseed in different forms has valuable effects and protects against cardiovascular disease, hypertension, diabetes, dyslipidemia, inflammation and some other complications. Flaxseed can serve as a promising candidate for the management of metabolic syndrome to control blood lipid levels, fasting blood sugar, insulin resistance, body weight, waist circumference, body mass and blood pressure.

Journal ArticleDOI
TL;DR: In this paper, the synthesis and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents were dissimilated, and tested compounds were found to kill and to inhibit the growth of a vast variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin, ampicillin, bifomazole and ketoconazole.
Abstract: AIMS AND OBJECTIVE The infectious disease treatment remains a challenging concern owing to the increasing number of pathogenic microorganisms associated with resistance to multiple drugs. A promising approach for combating microbial infection is to combine two or more known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents were dissimilated. MATERIALS AND METHODS The preparation of the substituted 5-benzylidene-2-thiazolyimino-4- thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi strains. Minimum inhibitory concentration and minimum bacterial concentration were both determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the title compounds. RESULTS PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone hybrids. All tested compounds were found to kill and to inhibit the growth of a vast variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin, ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective molecular target identification and revealed favorable interaction with the target enzymes E. coli MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active compounds was found toxic. CONCLUSION Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and may find a potential therapeutic use to eradicate infectious diseases.

Journal ArticleDOI
TL;DR: This study shows that TME features may serve as markers for evaluating response of SCLC cells to immunotherapy, and a group of genes that are highly associated with TME are identified.
Abstract: BACKGROUND Tumor microenvironment (TME) cells play important roles in tumor progression. Accumulating evidence show that they can be exploited to predict the clinical outcomes and therapeutic responses of the tumor. However, the role of immune genes of TME in small cell lung cancer (SCLC) is currently unknown. OBJECTIVE To determine the role of immune genes in SCLC. METHODS We downloaded the expression profile and clinical follow-up data of SCLC patients from Gene Expression Omnibus (GEO), and TME infiltration profile data of 158 patients using CIBERSORT. The correlation between TME phenotypes, genomic features, and clinicopathological features of SCLC was examined. A gene signature was constructed based on TME genes to further evaluate the relationship between molecular subtypes of SCLC with the prognosis and clinical features. RESULTS We identified a group of genes that are highly associated with TME. Several immune cells in TME cells were significantly correlated with SCLC prognosis (p<0.0001). These immune cells displayed diverse immune patterns. Three molecular subtypes of SCLC (TMEC1-3) were identified on the basis of enrichment of immune cell components, and these subtypes showed dissimilar prognosis profiles (p=0.03). The subtype with the best prognosis, TMEC3, was enriched with immune activation factors such as oncogene M0, oncogene M2, T cells follicular helper, and T cells CD8 (p<0.001). The TMEC1 subtype with the worst prognosis was enriched with T cells CD4 naive, B cells memory and Dendritic cells activated cells (p<0.001). Further analysis showed that the TME was significantly enriched with immune checkpoint genes, immune genes, and immune pathway genes (p<0.01). From the gene expression data, we identified four TME-related genes, GZMB, HAVCR2, PRF1 and TBX2, which were significantly associated with poor prognosis in both the training set and the validation set (p<0.05). These genes may serve as markers for monitoring tumor responses to immune checkpoint inhibitors. CONCLUSION This study shows that TME features may serve as markers for evaluating the response of SCLC cells to immunotherapy.

Journal ArticleDOI
TL;DR: Functional analysis of a competing endogenous RNA network constructed identified some essential immune functions, hematopoietic functions, osteoclast differentiation, and primary immunodeficiency as associated with neonatal sepsis.
Abstract: Background Neonatal sepsis is a serious and difficult-to-diagnose systemic infectious disease occurring during the neonatal period. Objective This study aimed to identify potential biomarkers of neonatal sepsis and explore its underlying mechanisms. Methods We downloaded the neonatal sepsis-related gene profile GSE25504 from the NCBI Gene Expression Omnibus (GEO) database. The differentially expressed RNAs (DERs) were screened and identified using LIMMA. Then, the functions of the DERs were evaluated using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, a competing endogenous RNA (ceRNA) network was constructed and functional analyses were performed. Results The initial screening identified 444 differentially expressed (DE)-mRNAs and 45 DElncRNAs. GO analysis showed that these DE-mRNAs were involved in immune response, defense response, and positive regulation of immune system process. KEGG analysis showed that these DE-mRNAs were enriched in 30 activated pathways and 6 suppressed pathways, and those with the highest scores were the IL-17 signaling pathway and ribosome. Next, 722 miRNAs associated with the identified lncRNAs were predicted using miRWalk. A ceRNA network was constructed that included 6 lncRNAs, 11 mRNAs, and 55 miRNAs. In this network, HCP5, LINC00638, XIST and TP53TG1 were hub nodes. Functional analysis of this network identified some essential immune functions, hematopoietic functions, osteoclast differentiation, and primary immunodeficiency as associated with neonatal sepsis. Conclusion HCP5, LINC00638, TP53TG1, ST20-AS1, and SERPINB9P1 may be potential biomarkers of neonatal sepsis and may be useful for rapid diagnosis; the biological process of the immune response was related to neonatal sepsis.

Journal ArticleDOI
TL;DR: In this paper, the polynomials of metal-organic networks have been analyzed and an analysis between the calculated various forms of polynomial and topological descriptors through the numeric values and their graphs is also comprised.
Abstract: AIM AND OBJECTIVE Metal-organic network (MON) is a special class of molecular compounds comprising of groups or metal ion and carbon-based ligand. These chemical compounds are examined employing one, two- or threedimensional formation of porous ore and subfamilies of polymers. Metal-organic networks are frequently utilized in catalysis for the parting & distillation of different gases and by means of conducting solid or super-capacitor. In various scenarios, the compounds are observed balanced in the procedure of deletion or diluter of the molecule and can be rebuilt with another molecular compound. The physical solidity and mechanical characteristics of the metal-organic network have attained great attention due to the mention properties. This study was undertaken to find the polynomials of MON. METHODS Topological descriptor is a numerical number that is utilized to predict the natural correlation amongst the physico-chemical properties of the molecular structures in their elementary networks. RESULTS After partitioning the vertices based on their degrees, we calculate different degree-based topological polynomials for two distinct metal-organic networks with an escalating number of layers containing both metals and carbon-based ligand vertices. CONCLUSION In the analysis of the metal-organic network, topological descriptors and their polynomials play an important part in modern chemistry. An analysis between the calculated various forms of the polynomials and topological descriptors through the numeric values and their graphs is also comprised.

Journal ArticleDOI
TL;DR: This document stores the name of the company and a description of its products and staff, as well as a brief description of the products and procedures used to produce them.
Abstract:

Journal ArticleDOI
TL;DR: QS mediated various potential target enzymes, its connection to AMR, and the corresponding QS biosynthetic target inhibitors can be derivatized to design and develop the next-generation antimicrobial agents are described.
Abstract: Objective The world is under the grasp of dangerous post-antibiotics and antimicrobials attack where common infections may become untreatable, leading to premature deaths due to antimicrobial resistance (AMR). While an estimated 7,00,000 people die annually due to AMR, which is a public health threat to all communities in different parts of the world regardless of their economic status; however, this threat is serious in low- and middle-income countries having lack of sanitation and health infrastructure. The 68th World Health Assembly endorsed the Global Action Plan on antimicrobial resistance. Consequently, many countries started drafting and committing to National Action Plans against AMR. As strong as National Action Plans are in terms of prescribing rational use of antimicrobials, infection control practices, and related public health measures, without strong healthcare systems, these measures will have a limited impact on AMR in developing countries. Methods The major reason for AMR is microbial quorum sensing (QS) that may strengthen the microbial community to generate inter-communication and virulence effects via quorum sensing mechanisms. Global stewardship to combat antimicrobial resistance aims to develop anti-quorum sensing compounds that can inhibit the biosynthetic pathway mediated different quorum sensing targets. Results It may pave an effective attempt to minimize microbial quorum sensing mediated antimicrobial resistance. The present review describes QS mediated various potential target enzymes, their connection to AMR, and finds out the corresponding QS biosynthetic target inhibitors. Conclusion These potential inhibitors can be derivatized to design and develop next-generation antimicrobial agents.

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TL;DR: Panax notoginseng may treat diabetic retinopathy through the mechanism of network pharmacological analysis, and the underlying molecular mechanisms were closely related to the intervention of angiogenesis, inflammation, and apoptosis.
Abstract: Background Panax notoginseng, a Chinese herbal medicine, has been widely used to treat vascular diseases. Diabetic retinopathy (DR) is one of the complications of diabetic microangiopathy. According to recent studies, the application of Panax notoginseng extract and related Chinese patent medicine preparations can significantly improve DR. However, the pharmacological mechanisms remain unclear. Therefore, the purpose of this study was to decipher the potential mechanism of Panax notoginseng treatment of DR using network pharmacology. Methods We evaluated and screened the active compounds of Panax notoginseng using the Traditional Chinese Medicine Systems Pharmacology database and collected potential targets of the compounds by target fishing. A multi-source database was also used to organize targets of DR. The potential targets as the treatment of DR with Panax notoginseng were then obtained by matching the compound targets with the DR targets. Using protein-protein interaction networks and topological analysis, interactions between potential targets were identified. In addition, we also performed gene ontology-biological process and pathway enrichment analysis for the potential targets by using the Biological Information Annotation Database. Results Eight active ingredients of Panax notoginseng and 31 potential targets for the treatment of DR were identified. The screening and enrichment analysis revealed that the treatment of DR using Panax notoginseng primarily involved 28 biological processes and 10 related pathways. Further analyses indicated that angiogenesis, inflammatory reactions, and apoptosis may be the main processes involved in the treatment of DR with Panax notoginseng. In addition, we determined that the mechanism of intervention of Panax notoginseng in treating DR may involve five core targets, VEGFA, MMP-9, MMP-2, FGF2, and COX-2. Conclusion Panax notoginseng may treat diabetic retinopathy through the mechanism of network pharmacological analysis. The underlying molecular mechanisms were closely related to the intervention of angiogenesis, inflammation, and apoptosis with VEGFA, MMP-9, MMP-2, FGF2, and COX-2 being possible targets.

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TL;DR: A convenient and rapid method has been developed for the synthesis of rhodanine and thiazolidine-2,4-dione (TZD) derivatives as efficient antimicrobial agents using a Deep Eutectic Ionic Liquids (DEILs) choline chloride urea under solvent-free condition.
Abstract: AIMS AND OBJECTIVE The magic scaffolds rhodanine and thiazolidine are very important heterocyclic compounds in drug design and discovery. Those are important heterocyclic compounds that have attracted a great deal of attention due to the fact that they exhibit a variety of bioactivities including antibacterial, antifungal, antiviral, antimalarial, and anti-inflammatory activities. These agents often exhibit selective toxicity. The goal of this study was molecular docking, green and solvent-free efficient synthesis of a new series of hetero/aromatic substituted rhodanine and thiazolidine analogues and then investigation of their antimicrobial activity. MATERIALS AND METHODS To a mixture of TZD or rhodanine (1 mmol) in the presence of ionic liquid ChCl/urea, various aldehyde (1 mmol) was added. After completion of the reaction, obtained crude compound was collected by filtration and products were recrystallized from ethanol. The binding-free energy between all synthesized compounds with 3EEJ protein (C. glabrata enzyme) were obtained by molecular docking studies. These compounds were evaluated using microdilution method against (ATCC 6538) and (ATCC 12228) Gram-negative, (ATCC 8739) and (ATCC 9027) as Gram-positive and (ATCC 1012), (ATCC 339), C. (ATCC 1057), (ATCC 503), (ATCC 340) and (ATCC 194) as fungi. RESULTS All of the acceptable products were determined by 1H NMR, 13C NMR, Mas and FT-IR spectroscopy. The binding-free energy between compounds 10a and 10b with 3EEJ protein were found to be -8.08 kcal/mol and -8.15 kcal/mol, respectively. These compounds having a heteroaromatic ring attached to the TZD or rhodanine core showed excellent antimicrobial activity with MIC values of 0.25-8 μg/mL (compound 10a) and 0.5-16 μg/mL (compound 10b) against the most tested fungi strains, Gram-positive and Gram-negative bacteria. CONCLUSION A convenient and rapid method has been developed for the synthesis of rhodanine and thiazolidine-2,4-dione (TZD) derivatives as efficient antimicrobial agents using a Deep Eutectic Ionic Liquids (DEILs) choline chloride urea under solvent-free condition. Among the newly synthesized compounds, (Z)-5-((quinoxalin-3-yl) methylene) thiazolidine-2, 4-dione (10a) and (Z)- 5- ((quinoxalin-3-yl) methylene)-2-thioxothiazolidin-one (10b) exerted the promising effect and these compounds can be considered to be further probed as inhibitors of cgDHFR enzyme.

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TL;DR: Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its anti-oxidant, anti-apoptotic properties and to protect the lung from severe destruction.
Abstract: BACKGROUND/AIM We aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia (BPD) induced by hyperoxia and lipopolysaccharide (LPS). MATERIALS AND METHODS Forty-two newborn Wistar rats born to spontaneous pregnant rats were divided into three groups: Hyperoxia (95% O2) + lipopolysaccharide (LPS) group, hyperoxia + LPS + astaxhantin group and control: no treatment group (21% O2). Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day to the fifth day. Histopathologic and biochemical evaluations including glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), total thiol, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1β) and caspase-3 activities were performed. RESULTS A better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group (p <0.001). In the histopathologic evaluation, the severity of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group, as well as decreased apoptosis (ELISA for caspase-3) (p <0.001). The biochemical analyses of lung tissues TAS, GSH, Total thiol levels were significantly higher in the astaxanthin treated group compared to hyperoxia + LPS group (p <0.05) while TOS, AOPP, LPO, 8-OHdG, MPO levels were significantly lower (p <0.001). In addition, unlike the hyperoxia + LPS group, TNF-α and IL-1β levels in lung tissue were significantly lower in the astaxanthin-treated group (p <0.001). CONCLUSION Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its antiinflammatory, anti-oxidant, anti-apoptotic properties and to protect the lung from severe destruction.

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TL;DR: Simulation using GROMACS has revealed LVNDGLNII epitope forms more stable complex with HLA molecule and will be useful in developing epitope-based Nipah virus vaccine.
Abstract: Aim and objective Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and spreads in humans through breathing resulting in an indication of encephalitis syndrome. In the current study, T cell epitopes with the NiV W protein antigens were predicted. Materials and methods Modelling of unavailable 3D structure of W protein followed by docking studies of respective Human MHC - class I and MHC - class II alleles predicted was carried out for the highest binding rates. In the computational analysis, epitopes were assessed for immunogenicity, conservation, and toxicity analysis. T - cell-based vaccine development against NiV was screened for eight epitopes of Indian - Asian origin. Results Two epitopes, SPVIAEHYY and LVNDGLNII, have been screened and selected for further docking study based on toxicity and conservancy analyses. These epitopes showed a significant score of -1.19 kcal/mol and 0.15 kcal/mol with HLA- B*35:03 and HLA- DRB1 * 07:03, respectively by using allele - Class I and Class II from AutoDock. These two peptides predicted by the reverse vaccinology approach are likely to induce immune response mediated by T - cells. Conclusion Simulation using GROMACS has revealed that LVNDGLNII epitope forms a more stable complex with HLA molecule and will be useful in developing the epitope-based Nipah virus vaccine.

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TL;DR: The derived model may be useful to predict the inhibitory activity of small molecules within the applicability domain of the model only based on the chemical structure information prior to their synthesis and testing.
Abstract: BACKGROUND: The quantitative structure-activity relationship (QSAR) approach is most widely used for prediction of biological activity of potential medicinal compounds. A QSAR model is developed by correlating the information obtained from chemical structures (numerical descriptors/independent variables) with the experimental response values (the dependent variable). METHODS: In the current study, we have developed a QSAR model to predict inhibitory activity of small molecule carboxamides against severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro enzyme. Due to the structural similarity of this enzyme with that of SARS-CoV-2, the causative organism of the recent pandemic, the former may be used for development of therapies against corona virus disease 19 (COVID-19). RESULTS: The final multiple linear regression (MLR) model was based on four two-dimensional descriptors with definite physicochemical meaning. The model was strictly validated using different internal and external quality metrics. The model showed significant statistical quality in terms of determination cofficient (R20.748, adjusted R2(R2adj 0.700), cross-validated leave-one-out Q2(Q20.628 and external predicted variance (R2pred 0.723). The final validated model was used for the prediction of external set compounds as well as to virtually design a new library of small molecules. We have also performed docking analysis of the most active and least active compounds present in the data set for comparative analysis and to explain the features obtained from the 2D-QSAR model. CONCLUSION: The derived model may be useful to predict the inhibitory activity of small molecules within the applicability domain of the model only based on the chemical structure information prior to their synthesis and testing.

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TL;DR: MAO-B inhibitors are well tolerated for the treatment of PD because of their pharmacokinetic properties and neuroprotective action and clinical evidence illustrated that MAO- B inhibitors are recommended as monotherapy and added on therapy to levodopa.
Abstract: Background One of the most prevalent neurodegenerative diseases with increasing age is Parkinson's disease (PD). Its pathogenesis is unclear and mainly confined to glutamate toxicity and oxidative stress. The dyskinesia and motor fluctuations and neuroprotective potential are the major concerns which are still unmet in PD therapy. Objective This article is a capsulization of the role of MAO-B in the treatment of PD, pharmacological properties, safety and efficiency, clinical evidence through random trials, future therapies and challenges. Conclusion MAO-B inhibitors are well tolerated for the treatment of PD because of their pharmacokinetic properties and neuroprotective action. Rasagiline and selegiline were recommended molecules for early PD and proven safe and provide a modest to significant rise in motor function, delay the use of levodopa and used in early PD. Moreover, safinamide is antiglutamatergic in action. When added to Levodopa, these molecules significantly reduce the offtime with a considerable improvement of non-motor symptoms. This review also discusses the new approaches in therapy like the use of biomarkers, neurorestorative growth factors, gene therapy, neuroimaging, neural transplantation, and nanotechnology. Clinical evidence illustrated that MAOB inhibitors are recommended as monotherapy and added on therapy to levodopa. A large study and further evidence are required in the field of future therapies to unwind the complexity of the disease.

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TL;DR: An overview of the synthetic protocols employed to prepare different classes of MAO-A inhibitors is provided, which provides a valuable tool for the development of new class of various selective MAO -A inhibitors for the treatment of depression and other anxiety disorders.
Abstract: Background Monoamine oxidases (MAOs) play a crucial role during the development of various neurodegenerative disorders. There are two MAO isozymes, MAO-A and MAO-B. MAO-A is a flavoenzyme, which binds to the outer mitochondrial membrane and catalyzes the oxidative transformations of neurotransmitters like serotonin, norepinephrine, and dopamine. Materials and methods Focus on synthetic studies has culminated in the preparation of many MAOA inhibitors, and advancements in combinatorial and parallel synthesis have accelerated the developments of synthetic schemes. Here, we provided an overview of the synthetic protocols employed to prepare different classes of MAO-A inhibitors. We classified these inhibitors according to their molecular scaffolds and the synthetic methods used. Results Various synthetic and natural derivatives from a different class of MAO-A inhibitors were reported. Conclusion The review provides a valuable tool for the development of a new class of various selective MAO-A inhibitors for the treatment of depression and other anxiety disorders.