Showing papers in "Medicinal Chemistry in 2016"
TL;DR: Cucurbita pepo is widely used like food and in folk medicine around the world as mentioned in this paper, it is also used extensively as a hypoglycaemic agent.
Abstract: Cucurbita pepo, is widely used like food and in folk medicine around of the world. This aims a comprehensive of the pharmacological, chemical constituents, and clinical uses. Also have been identified the medicinally important phyto-constituents belonging mainly to cucurbitosides, multiflorane-type triterpenoids, carotenoids, ent-kauranetype diterpene, and cucurbitaglycosides. Extracts and metabolites of this plant, particularly those from seeds and fruits possess useful pharmacological activities. A survey of the literature shows C. pepo, is mainly known for its improvement in prostatic hiperplasia (BPH), urinary dysfunction and cytotoxic properties, also has also been used extensively as a hypoglycaemic agent. Many pharmacological studies have demonstrated hepatoprotection, inhibit benign prostatic hiperplasia, antioxidant, anticancer, antimicrobial, antiinflamatory, antidiabetic, and antiulcer activities supporting its traditional uses.
101 citations
TL;DR: Circulating miRNAs within blood and other biofluids may be characterized and used as non-invasive, diagnostic biomarkers that facilitate the early detection of disease and potentially the continual monitoring of disease progression for NDDs such as AD and PD.
Abstract: Detection of biomarkers for neurodegenerative disorders (NDDs) within brain tissues of Alzheimer's disease (AD) and Parkinson's disease (PD) patients has always been hampered by our inability to access and biopsy tissue of key brain regions implicated in disease occurrence and progression. Currently, diagnosis of NDDs is principally based on clinical observations of symptoms that present at later stages of disease progression, followed by neuroimaging and, possibly, CSF evaluation. One way to potentially detect and diagnose NDDs at a far earlier stage is to screen for abnormal levels of specific disease markers within the peripheral circulation of patients with NDDs. Increasing evidence suggests that there is dysregulation of microRNAs (miRNAs) in NDDs. Peripheral blood mononuclear cells, as well as biofluids, such as plasma, serum, urine and cerebrospinal fluid, contain miRNAs that can be identified and quantified. Circulating miRNAs within blood and other biofluids may thus be characterized and used as non-invasive, diagnostic biomarkers that facilitate the early detection of disease and potentially the continual monitoring of disease progression for NDDs such as AD and PD. Plainly, such a screen is only possible with a clear understanding of which miRNAs change with disease, and when these changes occur during the progression of AD and PD. Such information is becoming increasingly available and, in the near future, may not only support disease diagnosis, but provide the opportunity to evaluate therapeutic interventions earlier in the disease process.
58 citations
TL;DR: This review is devoted to broaden the understanding regarding atherosclerosis and the central role of calcium in the development of the condition.
Abstract: In the beginning, atherosclerosis was considered to be the result of passive lipid accumulation in the vascular walls. After tremendous technological advancements in research, we are now able to almost admire the complexity of the atherosclerotic process. Atherosclerosis is a chronicinflammatory condition that begins with the formation of calcified plaque, influenced by a number of different factors inside the vascular wall in large and mid-sized arteries. Calcium mineralization of the lumen in the atherosclerotic artery promotes and solidifies plaque formation causing narrowing of the vessel. Soft tissue calcification associated with tissue denegation or necrosis is a passive precipitation event. The process of atherogenesis is mainly driven by CD4+ T cells, CD40L, macrophages, foam cells with elevated transcription of many matrix metalloproteinases, osteoblasts, cytokines, selectins, myeloperoxidases, vascular adhesion molecules (VCAM), and smooth muscle cells. Our knowledge in the genesis of atherosclerosis has changed dramatically in the last few years. New imaging techniques such as intravascular ultrasound or IVUS have made possible to investigate atherosclerosis in early stages. Arterial calcification emerges from two different types, the medial-elastin dependent and the intimal, both of which are directly related to atherosclerosis due to osteoblast differentiation of vascular smooth muscle cells. The deposition of minerals in the form of calcium (Ca(2+)) initially emerges from the inorganing mineral octacalcium phosphate [Ca8H2(PO4)6.5H2O] to the form of Hydroxylapatite [Ca10(PO4)6(OH)2]. This review is devoted to broaden the understanding regarding atherosclerosis and the central role of calcium in the development of the condition.
42 citations
TL;DR: Progress on research conducted to understand the antimicrobial activity and related bioactive properties of Moringa oleifera compounds are described, and the potential use of Moreda o leiferain the control of pathogenic microbes is discussed.
Abstract: Moringa oleifera is a kind of woody tree traditionally used as a nutritional source and as a medicinal plant. It grows wild in the tropical and subtropical areas of Asia, Africa and the Middle East. In China, Moringa oleifera trees are planted at a large scale in Yunnan, Guangdong and Guangxi Provinces. As a nutritional and medicinal plant, Moringa oleiferais a rich source of bioactive compounds with diverse pharmacological activities. It has been widely used in the treatment of certain diseases as a traditional medicinal herb. Antimicrobial activity is the most studied property of Moringa oleifera. Many studies have shown that the leaf, flower, bark, root, seed, and nearly all types of Moringa oleiferatissues exhibit antimicrobial activity including antibacterial, antifungal, antiviral and antiparasitic activity. This review describes progress on research conducted to understand the antimicrobial activity and related bioactive properties of Moringa oleifera compounds, and discusses the potential use of Moringa oleiferain the control of pathogenic microbes.
42 citations
TL;DR: The results suggest that P-CA may inhibit the production of inflammatory cytokines induced by LPS through blocking NF-kB and MAPKs signaling pathways, which further support the anti-inflammatory and immunomodulatory potential of P- CA in different models of inflammation.
Abstract: P-coumaric acid (p-CA), which was widely found in nutritious plant foods, has various anti-inflammatory effects in vivo. In order to clarify the anti-inflammatory mechanisms, the effects on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW264.7 macrophage cells were examined by pretreated with P-CA (10-100 μg/ml). P-CA signii¬cantly inhibited iNOS, COX-2, IL-1β and TNF-α expression at mRNA and/or protein level. Furthermore, P-CA suppressed the phosphorylation of IκB and ERK1/2. The above results suggest that P-CA may inhibit the production of inflammatory cytokines induced by LPS through blocking NF-kB and MAPKs signaling pathways, which further support the anti-inflammatory and immunomodulatory potential of P-CA in different models of inflammation.
41 citations
TL;DR: The platelet derived growth factor (PDGF), which is expressed by many SNC cells, including astrocytes, is an important molecule that has shown neuroprotective potential, improvement of wound healing, regulation of calcium metabolism and mitochondrial function.
Abstract: Astrocytes exert multiple functions in the brain such as the development of blood-brain barrier characteristics, the promotion of neurovascular coupling, attraction of cells through the release of chemokines, clearance of toxic substances and generation of antioxidant molecules and growth factors. In this aspect, astrocytes secrete several growth factors (BDNF, GDNF, NGF, and others) that are fundamental for cell viability, oxidant protection, genetic expression and modulation of metabolic functions. The platelet derived growth factor (PDGF), which is expressed by many SNC cells, including astrocytes, is an important molecule that has shown neuroprotective potential, improvement of wound healing, regulation of calcium metabolism and mitochondrial function. Here we explore some of these astrocyte-driven functions of growth factors and their possible therapeutic uses in the context of neurodegeneration.
34 citations
TL;DR: This review is prepared to give insight into 5-ASA chemistry, anti-inflammatory activity, in particular, for treatment of IBD.
Abstract: Salicylic acid (SA) derivatives are widely used for treatment of various diseases. Acetylsalicylic acid represents the most widely used drug in the world, 4-Aminosalicylic acid (4-ASA) was historically used as a systemic antituberculosis drug as well as diflunisal is a strong pain killer and antipyretic. 5-Aminosalicylic acid (5-ASA) which had been synthesized at the end of 19th century and employed first for the production of azo dyes, was then identified as a very valuable medicinal agent as well as part of many biologically active agents. 5-ASA is not metabolized to salicylic acid for pharmacological activity. It is not considered a true salicylate. In contrary to other salicylates, 5-ASA doesn’t induce upper gastrointestinal (GI) side effects. Moreover, It was found, especially, useful for treatment of inflammatory bowel diseases (IBD). It is unique among salicylates and has a broad specrum of biological activities including, anti-inflammatory, analgesic, neuroprotective and antitumor. Since we are interested in this compound and its derivatives, we prepared this review to give insight into its chemistry, anti-inflammatory activity, in particular, for treatment of IBD. Different approaches for colonic targeting of 5-ASA w ill be covered with emphasis on chemical methods as well as its proposed mechanisms of action.
33 citations
TL;DR: In this article, the antimicrobial properties of Artemisia herba-alba Asso essential oil obtained by hydrodistillation growing in Algeria (Djelfacityof south Algeria) were investigated by GC/FID and GC-MS.
Abstract: In the recent decades, antimicrobial plant products have gained special interest because of the resistance to antibiotics that some micro-organisms have acquired. Aromatic and medicinal plants are an important source of bioactive molecules, especially in volatile extracts, that are considered among the most important antimicrobial agents present in these plants. Volatile components of Artemisia herba-alba Asso essential oil obtained by hydrodistillation growing in Algeria (Djelfacityof south Algeria) were investigated by GC/FID and GC-MS. The major components were found to be camphor (39.5%), chrysanthenone (10.38%), 1,8-cineole (8.6%), α-thujone (7.03%), Borneol (3.35%) and bornyl acetate (2.52%). The essential oil has been tested for antimicrobial activity against Gram-negative and Gram-positive bacteria. Inhibition of growth was tested by the agar diffusion method. The Minimal Inhibitory Concentration (MIC) was determined by the method of agar dilution.
32 citations
TL;DR: The observed antimicrobial activity of the extract, PLE, may be due in large proportion to its major constituent, geraniin, which may act as microbiostatic agents.
Abstract: Microbial resistance to existing antimicrobial agents remains a global challenge. In recent years, there has been a significant upsurge in the search for newer antimicrobial agents from nature with plants becoming the major focus in most parts of the world due to the vast availability of plants, which have not been screened for their antimicrobial activity. Hence, the study investigates the antimicrobial properties of aqueous aerial part extract of Phyllanthus muellerianus (PLE) and its major constituent, geraniin. The agar well diffusion and micro-dilution methods as well as time-kill kinetic studies were used to determine the antimicrobial activity of PLE and geraniin against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis NCTC 10073, Streptococcus pyogenes (clinical isolate) and Candida albicans (clinical isolate). The mean zones of growth inhibition for PLE and geraniin were in the range of 12.0 ± 0.0 to 22.7 ± 0.3 and 12.0 ± 0.0 to 21.6 ± 0.3 mm, respectively. MIC of both PLE and geraniin ranged from 0.31 to 5 and 0.08 to 1.25 mg/mL (90 to 1310 μM), respectively whiles the minimum cidal concentrations were 5.0 to 50.0 and 2.5 to 10 mg/mL (2.62 to 10.5 mM), respectively. The time-kill kinetics study showed that PLE and geraniin may act as microbiostatic agents. Preliminary phytochemical screening of PLE showed the presence of alkaloids, glycosides, saponins, tannins, flavonoids and terpenoids. The observed antimicrobial activity of the extract, PLE, may be due in large proportion to its major constituent, geraniin.
30 citations
TL;DR: In this paper, the authors reported the synthesis of novel series of 5]-1,3-bis (4- substituted phenyl) prop-2-en-1-ylidene]- 2-thioxodihydropyrimidine-4,6(1H, 5H)-diones (5a-k).
Abstract: In this paper we reported the synthesis of novel series of 5-[1,3-bis (4- substituted phenyl) prop-2-en-1-ylidene]- 2-thioxodihydropyrimidine-4,6(1H, 5H)-diones (5a-k). The target compounds were synthesized by the Knoevenagel condensation of different chalcones (3a-k) with thiobarbituric acid using acetic acid as a catalyst in ethanol. These compounds were screened for their antimicrobial and antioxidant activities. From antimicrobial activity results it was found that compounds 5e, 5i and 5k displayed good antibacterial and antifungal activity against all tested strains. Further, the selected compounds were studied for docking using the enzyme, Glucosamine-6-phosphate synthase and the compounds 5a, 5e and 5k have emerged as an active antimicrobial agents with least binding energy (-4.52 and -4.41 kJ mol-1). Compounds 5c and 5f showed promising free radical scavenging and Fe+2 ion chelating activity.
28 citations
Abstract: Background: Ziziphus spina-christi is a tropical evergreen tree of Sudanese origin. The plant is commonly used in ethno-medicine for the treatment of many diseases such as malaria, digestive disorders, weakness, hepatic diseases, obesity, urinary problems, diabetes, skin infections, fever, diarrhea and insomnia. However, the pharmaceutical properties and bioactive compounds present in Z. spina-christi are still unknown. Therefore, the aim of the study was to significantly improve and deepen our knowledge about the phenolic composition of Z. spina-christi leaf extracts as well as their antibacterial and potential cytotoxic effects.
Methods: The phytochemical profile of the known compounds in the methanol/water (7:3 v/v) extract of Z. spinachristi leaves were tentatively assigned on the basis of reported analytical data from three to four pieces of independent methods including retention time (tR), UV/Vis spectroscopy, high resolution mass spectrometry (HR-MS) and tandem mass spectrometry (MSn). Four bioactive compounds were purified via preparative-HPLC and identified by means of HPLC-ESI-TOF, HPLC-ESI-MSn, 1H-NMR, 13C-NMR, literature data and authentic reference standards. Antibacterial activities of aqueous and methanol leaf extracts were carried out with six bacterial strains (Bacillus subtilis, Bacillus aquimaris, Clavibacter michiganensis, Escherichia coli, Erwinia amylovora, and Pseudomonas syringae) using an agar diffusion assay. Cytotoxic effects towards the human epidermal keratinocyte cell line HaCaT and rat intestine epithelial IEC-6 cells was assess by cytoskeletal and plasma membrane integrity or analyses of mitochondrial and proliferative activities.
Results: We tentatively assigned fifty-seven phenolic compounds (fifty-two of them are known) to their regioisomeric level in the methanol/water extract of Z. spina-christi leaves. To our knowledge 45 of them were not reported previously in Z. spina-christi and five for the first time in nature. Highly glycosylated flavonoids, proanthocyanidins, and chlorogenic acids were identified as the major components. Preparative-HPLC let to the isolation of four known phytochemicals including quercetin 3-O-(6-O-rhamnosyl-glucoside) (rutin) 26, quercetin 3-O-(2-O-rhamnosyl-arabinoside) 27, phloretin 3',5' di-C-glucoside 39 and quercetin 3-O-(2,6-di-O-rhamnosyl-glucoside) 50. Regarding the antimicrobial assays, the methanol extracts of the plant were found to show higher activity than the aqueous extracts indicating hydrophobic substances of Ziziphus leaves exerting antibacterial activity. The extracts revealed no cytotoxic effects towards the HaCaT or IEC-6 cells.
Conclusions: Several previously known and unknown compounds were indentified in Z. spina-christi leaf extracts. The plant possesses strong antimicrobial activity and no toxicity. Our results therefore suggest that Z. spina-christi extracts might be potentially suitable for topical applications and support the use of the plant in traditional medicine to treat infectious diseases.
TL;DR: The recent developments in 4-aminoquinoline derived new analogs and insight into design and development of new antimalarials are discussed.
Abstract: Malaria is a major health problem and Plasmodium falciparum strain resistance to existing antimalarials drugs made the current approach inadequate for treatment of malaria. Drug development directed against malaria is generally targeting blood schizonts. However, to prevent relapse, tissue schizontocides are recommended to clean residual infection in the tissues. In spite of the available drugs, malarial chemotherapy is still insufficient and therefore new strategies are being explored to fill the gaps. The new approaches are being used to generate new compounds as well as combinations of drugs for development of effective and safe antimalarial therapy. This review discusses the recent developments in 4-aminoquinoline derived new analogs and insight into design and development of new antimalarials.
TL;DR: This work presents an inclusive outline of parallelism between AD and VaD by exploring the potential commonalities at the mechanistic and therapeutic levels and suggests that the lifestyle changes and medications prescribed to curb one of these diseases may also help curb the other.
Abstract: The two most common forms of dementia are Alzheimer's disease (AD) followed by vascular dementia (VaD), together accounting for a whopping 60-80% of total dementia cases worldwide. Even though these diseases are recognized as 'common', they still remain underdiagnosed. Recent research suggests that AD and VaD are closely intertwined. The symptoms of AD and VaD can be similar and the two conditions can occur simultaneously. A large number of patients diagnosed with AD have also been reported with VaD-caused brain damage. Moreover, both the diseases have been reported to have similar risk factors. The overlap between these diseases is important because the lifestyle changes and medications prescribed to curb one of these diseases may also help curb the other. In the present review, we present an inclusive outline of parallelism between AD and VaD by exploring the potential commonalities at the mechanistic and therapeutic levels.
TL;DR: Recent advances in identification of the molecular mechanisms involved in Platelet activation upon stimulation with various agonists in vitro and in vivo are described, along with potential targets for pharmacologic interventions in disease states.
Abstract: Platelets are involved in haemostasis and vessel integrity under physiologic conditions, and in thrombosis under disease states. Platelet activation upon stimulation with various agonists in vitro and in vivo, is strongly dependent on an increase of intracellular Ca(2+) concentration. The latter results from Ca(2+) release by the dense tubular system (DTS), and Ca(2+) entry from the extracellular space. Recent advances in identification of the molecular mechanisms involved in these processes are described in this review, along with potential targets for pharmacologic interventions in disease states.
TL;DR: In this paper, the authors report the recent progress (2010-2016) on the biological activities of some monodentate, bidentate, tridentate and tetradente compounds based on pyrazole moieties and containing NCN bonds which connecting between the pyrazoles and amine unit.
Abstract: Pyrazole derivatives have their own importance in aromatic organic heterocycle family. Application of these derivatives in chemistry and biology has attracted increasing interest occupy a unique place in field of medicinal chemistry due to their wide spectrum of biological activities. There are known for their anticancer, antiviral, antibacterial, antifungal, analgesic and anti-inflammatory and activities and so on. Due to the importance of this chemical skeletons, the present review reports the recent progress (2010-2016) on the biological activities of some monodentate, bidentate, tridentate and tetradente compounds based on pyrazole moieties and containing NCN bonds which connecting between the pyrazole and amine unit.
TL;DR: The results showed that the centrifugation method can be used for separation of free drug, a critical step in measuring encapsulation efficiency, and the EE of three batches of CPT-11/DSPE-mPEG2000 micelles was 90.0% ± 1.0%.
Abstract: Herein we report development and validation of the method for evaluating the encapsulation efficiency of a micelle-based nanosystem composed of irinotecan hydrochloride (CPT-11) and an amphiphilic molecule DSPEmPEG2000. The results showed that the centrifugation method can be used for separation of free drug, a critical step in measuring encapsulation efficiency, and the EE of three batches of CPT-11/DSPE-mPEG2000 micelles was 90.0% ± 1.0%. The results also indicated that the conditions used in the process have to be optimized to acquire reliable data.
TL;DR: It is found that these tetradentate ligands act specifically as antifungal agents and lack antibacterial activity.
Abstract: A new library of N,N,N’,N’ -tetradentate pyrazoly compounds containing a pyrazole moiety was synthesized by the condensation of (3,5-dimethyl-1H-pyrazol-1-yl)methanol 2a or (1H-pyrazol-1-yl)methanol 2b with a series of primary diamines in refluxed acetonitrile for 6h. The antifungal activity against the budding yeast Saccharomyces cerevisiae, as well as the antibacterial activity against Escherichia coli of these new tetradentate ligands were studied. We found that these tetradentate ligands act specifically as antifungal agents and lack antibacterial activity. Their biological activities depend on the nature of the structure of the compounds.
TL;DR: The present review highlights the phytopharmacological and different traditional use of G. asiatica which is mentioned in ancient Ayurvedic texts and stimulates the researchers and scientists for further research on the medicinally important fruit commonly called Falsa.
Abstract: Since ancient time, India is a well known subcontinent for medicinal plants where diversity of plants is known for the treatment of many human disorders. Grewia asiatica is a dicot shrub belonging to the Grewioideae family and well known for its medicinally important fruit commonly called Falsa. G. asiatica, a seasonal summer plant is distributed in the forest of central India, south India, also available in northern plains and western Himalaya up to the height of 3000 ft. Fruits of G. asiatica are traditionally used as a cooling agent, refreshing drink, anti-inflammatory agent and for the treatment of some urological disorders. Recent advancement of Falsa researches concluded its antimicrobial and anti-diabetic activity. Since ancient time medicinal plants are traditionally used for the treatment of different diseases G. asiatica fruit is the edible and tasty part of the plant, now considered as a valuable source of unique natural product for the development of medicines which are used in different disease conditions like anti-diabetic, anti-inflammatory, anti-cancerous and antimicrobial. Now a days, G. asiatica is being used in different Ayurvedic formulation for the cure of different types of diseases. Different pharmacological investigations reveal the presence of phenols, saponnins, flavonoids and tannins compound in the fruits. Present review highlights the phytopharmacological and different traditional use of G. asiatica which is mentioned in ancient Ayurvedic texts. This review stimulates the researchers and scientists for further research on G. asiatica.
TL;DR: Results indicate that compound-4 (N-(5-(1-(4-isobutyl-phenyl)-ethyl)-1,3,4-thiadiazol-2-yl)-acetamide) exhibited highest analgesic activity, where as compound-5 possessed 65.5% activity.
Abstract: A series of novel substituted 2-amino-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazoles were designed, synthesized and evaluated as anti-inflammatory and analgesic agents. Compounds were characterized by elemental and spectroscopic analysis. Compounds possessing significant activities were screened for ulcerogenic activity. Compound-5 (2-(4-isobutylphenyl)-N-(5-(1-(4- isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-yl)-propanamide) produces significant in vitro antiinflammatory activity (72.5%) as compared to ibuprofen (47.7%), while compound-3f (2-(Ncyclohexyl- N-methylamino)-N-(5-(1-(4-isobutylphenyl)-ethyl)-1,3,4-thiadiazol-2-yl)-acetamide) showed 64.1 % activity. Results indicate that compound-4 (N-(5-(1-(4-isobutyl-phenyl)-ethyl)-1,3,4-thiadiazol-2-yl)-acetamide) exhibited highest analgesic activity (69.8%), where as compound-5 possessed 65.5% activity. Structure based drug design was also investigated to reveal the mechanism of action and specificity of our compounds against COX-2 enzyme. Anti-inflammatory activity and ulcerogenic potential were in agreement with the molecular modeling studies carried out on cycloxygenase enzyme.
TL;DR: A brief survey of the main characteristics, structures, advantages and recent advances on polymer-clay composites (PCCs) and polymerclay nanocomposites (PCN) for environmental applications is presented in this article.
Abstract: Nowadays, many organic contaminants, some of them byproducts from other types of reactions such as dyes or phenolic compounds, or even endocrine disruptors, pharmaceuticals, and personal care products, have been detected in wastewater. Most of them are not controlled and, possibly, can cause harmful effects in aquatic life at environmentally significant concentrations. It is noteworthy, that conventional wastewater treatment plants are not always effective for the removal of these classes of pollutants and so further water treatments are necessary. Therefore, many processes have been investigated for advanced treatment of these effluents as well as for organic pollutants degradation; among these, adsorption process has been used to remove them from wastewater. In addition, there has been a considerable development of new materials with interesting properties, both at large scale and at micro- or nanoscale. Some of these materials are more efficient than others, due to their dimensions in these latter scales, in different kind of applications; specifically, in the field of water treatment. This review is a brief survey of the main characteristics, structures, advantages and recent advances on polymer-clay composites (PCC’s) and polymer-clay nanocomposites (PCN’s), for environmental applications. In the first part are included some basic concepts: composite materials have components with contrasting yet complementary properties; e.g., organoclays which serve as reinforcement of polymeric matrices and give them a larger contact surface and greater mechanical strength. In particular, PCN’s are materials that are used in different applications, for instance to model the morphology of partially crystalline polymers, to remove pollutants from water effluents, to employ them in adsorption processes from water streams, etc. Finally, in the second part, some of developments in the synthesis and applications of these novel materials are discussed; in particular, applications on the field of water pollutants removal through the adsorption process.
TL;DR: Two new limonoids, named rubescins D-E (1-2) along with eight known compounds, including five havanensin type limonoid, TS1, TS3, rubescin A-C and three known phytosterols, β-sitosterol, stigmasterol and its 3β-O-glucopyranoside derivative were isolated from the roots and stem bark of Trichilia rubescens, collected from Cameroon.
Abstract: Two new limonoids, named rubescins D-E (1-2) along with eight known compounds, including five havanensin type limonoids, TS1 (3), TS3 (4), rubescins A-C (5-7) and three known phytosterols, -sitosterol, stigmasterol and its 3-O-glucopyranoside derivative were isolated from the roots and stem bark of Trichilia rubescens, collected from Cameroon. The structures of the new compounds were determined by detailed analyses of 1D and 2D NMR spectra, in combination with high-resolution mass spectrometry data and by comparison with related data from literature. Anti-plasmodial activities of some of the isolated limonoids 1, 2, 4, 6 and 7 were evaluated against erythrocytic stages of strain 3D7 Plasmodium falciparum. Compounds 2 and 4 exhibited significant anti-plasmodial in vitro activity with IC50 values of 1.13 and 0.79 M, respectively.
TL;DR: Many of the investigated compounds showed potent activity against all tested microbial species, and provided a foundation for the synthesized compounds to serve as a platform for further design and development of more potent antimicrobial agents.
Abstract: Background: The antimicrobial activity of a synthesized series of 28 2-thioxobenzo[ g]quinazolin-4(3H)-one derivatives was evaluated in vitro against five Gram-positive bacteria, including Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. The antibacterial activity was extended to include five Gramnegative bacteria: Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Enterobacter cloacae. Furthermore, the antifungal activity was evaluated against 10 fungal strains, including Aspergillus fumigatus, Syncephalastrum racemosum, Geotricum candidum, Candida albicans, Aspergillus niger, Cryptococcus neoformans, Candida tropicalis, Penicillium expansum, Microsporum canis and Trichophyton mentagrophytes. Methods: The agar well diffusion method was adopted against Gram-positive and Gram-negative bacteria and fungi, using ampicillin, gentamicin and amphotericin B as reference drugs, respectively. Results: The findings of the antibacterial studies revealed that most of the tested compounds possess strong activity against both bacterial species. Compounds 8 and 23 were the most active on Grampositive bacteria, while several compounds demonstrated significant antibacterial activity on Gramnegative bacteria, especially Escherichia coli. Furthermore, several compounds showed strong antifungal activity against many of the investigated fungi. The obtained results were reinforced by determination of the minimum inhibitory concentration for the active compounds against Grampositive and Gram-negative bacteria, as well as fungi, compared to the reference drugs. Conclusion: Many of the investigated compounds showed potent activity against all tested microbial species. The discovery has provided a foundation for the synthesized compounds to serve as a platform for further design and development of more potent antimicrobial agents.
TL;DR: All mice which were immunized with liposome-lipopeptide delivery system elicited high levels of systemic and mucosal antibodies, which were discernably higher than those induced with the help of commercial adjuvant.
Abstract: Background: Group A streptococcus (GAS) is an exclusively human pathogenic bacteria. A delay in treatment of GAS infection often lead to severe diseases such as rheumatic heart disease which attributes to hundreds of thousands deaths annually. For the past few decades, the quest for a commercial GAS vaccine has been futile. Currently one of the most investigated strategies to develop vaccine against GAS includes the use of conserved epitopes from major virulent factor of GAS, M-protein. Methods: In this study, cationic liposomes of various sizes (70 nm to 1000 nm) were prepared with dimethyldioctadecylammonium bromide (DDAB) encapsulating lipopeptide bearing M-protein derived B-cell epitope (J14). Results: Smaller liposomes induced higher antibody titres, though the differences between groups were not statistically significant. Conclusion: Nonetheless, all mice which were immunized with liposome-lipopeptide delivery system elicited high levels of systemic (IgG) and mucosal antibodies (IgA), which were discernably higher than those induced with the help of commercial adjuvant (cholera toxin B subunit).
TL;DR: The author describes the development of prodrugs targeted to specific cell types and polymeric nanocarriers used as fluorescent probes which offer advantages in the integration of “smart” features of fluorescent dyes into synthetic materials.
Abstract: This review highlights the role of fluorescent dyes as active “molecular photoswiches” focusing on the application in bioimaging and anticancer therapies in the field of therapeutic delivery. The author describes the development of prodrugs targeted to specific cell types and polymeric nanocarriers (capsules, micelles and silica nanoparticles) used as fluorescent probes which offer advantages in the integration of “smart” features of fluorescent dyes into synthetic materials. The incorporation of biologically responsive components that cleave upon changes in pH or light irradiation is fundamental to the successful design of such carriers with capabilities to load and release therapeutics specifically at a target site.
TL;DR: Harmine 1 was extracted from the seeds of Peganum harmala and a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides, which were shown to be inactive against the XOD enzyme.
Abstract: Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by (1)H NMR, (13)C NMR and HRMS. The evaluation of their anti-acetylcholinesterase (AChE), anti-5-lipoxygenase (5-LOX), anti-xanthine oxidase (XOD) and anticancer activities were studied in vitro against AChE, 5-LOX and XOD enzymes, respectively, and in HTC-116, MCF7 and OVCAR-3 cancer cell lines. The prepared derivatives were shown to be inactive against the XOD enzyme (0-38.3 ± 1.9% at 100 µM). Compound 2 exhibited the best anti-AChE activity (IC50=1.9 ± 1.5 µM). Derivatives 3a, 3b and 3d had moderate cytotoxic activities (IC50=5.0 ± 0.3 µM (3a) and IC50=6.3 ± 0.4 µM (3b) against HCT 116 cells, IC50=5.0 ± 1.0 µM (3d) against MCF7 cells).
TL;DR: This review attempts to summarize the recent Structure Activity Relationship (SAR) studies of aporphine alkaloids specifically at the serotonin receptor system and concludes that aporPHines have great potential to be developed as potent serotonergic ligands.
Abstract: The aporphine alkaloids are known to have affinities as the dopaminergic, adrenergic and serotonergic receptor system. Hence the aporphine template can be considered as a privileged scaffold for the design of selective monopotent as well as multi-potent Central Nervous System (CNS) ligands. This review attempts to summarize the recent Structure Activity Relationship (SAR) studies of aporphine alkaloids specifically at the serotonin receptor system. Based on the obtained SAR information it can be concluded that aporphines have great potential to be developed as potent serotonergic ligands.
TL;DR: The inhibition study of these synthesized molecules was carried out to discover their possible therapeutic effect as target for Alzheimer’s disease.
Abstract: In the present work, a new series of different 4-{[4-(2-furoyl)-1-piperazinyl]methyl}-N-(substituted-phenyl) benzamides (5a-h) have been synthesized as possible therapeutic agents for the treatment of Alzheimer’s disease. The structural confirmation of all the synthesized compounds was carried out by their IR, 1H-NMR and EI-MS spectral data. Enzyme inhibition activity was performed against butyrylcholinestrase enzyme, which revealed that, 4-{[4-(2-furoyl)-1- piperazinyl]methyl}-N-(4-ethylphenyl)benzamide (5b) showed excellent IC50 value 0.82 ± 0.001 μM relative to Eserine, a reference standard having IC50 value of 0.85 ± 0.0001 μM. The enhanced potential of this molecule may be attributed to the 4-ethylphenyl group. As the cholinesterase enzyme inhibitors are good targets for Alzheimer’s disease, therefore, the inhibition study of these synthesized molecules was carried out to discover their possible therapeutic effect as target for aforesaid disease.
TL;DR: The intention of this review is to demonstrate the exclusive ability of MAOS in water as solvent or as co-solvent, focusing on medicinal chemistry processes leading to interesting nitrogen containing heterocycles with potential pharmaceutical applications.
Abstract: Background: Green chemistry is a discipline of great interest in medicinal chemistry. It involves all fields of chemistry and it is based on the principle to conduct chemical reactions protecting the environment at the same time, through the use of chemical procedures able to avoid pollution. In this context, water as solvent is a good choice because it is abundant, nontoxic, non-caustic, and non-combustible. Even if microwave assisted organic reactions in conventional solvents have quickly progressed, in the recent years medicinal chemists have focused their attention to processes deemed not dangerous for the environment, using nanotechnology and greener solvents as water. Objective: Several reports of reaction optimizations and selectivities, demonstrating the capability of microwave to allow the obtaining of increased yields have been recently published using water as solvent. In this review, we selected the available knowledge related to microwave assisted organic synthesis in aqueous medium, furnishing examples of the newest strategies to obtain useful scaffolds and novel derivatives for medicinal chemistry purposes. Conclusion: The intention of this review is to demonstrate the exclusive ability of MAOS in water as solvent or as co-solvent. For this purpose we report here the most representative applications of MAOS using water as solvent, focusing on medicinal chemistry processes leading to interesting nitrogen containing heterocycles with potential pharmaceutical applications.
TL;DR: All the synthesized derivatives of Diindolyl methanes show moderate anticancer activities against human breast cell line MCF7, good antioxidant andα-amylase inhibitory activities using DPPH and α-amymylase assay respectively.
Abstract: Several Diindolyl alkanes and their derivatives have been isolated from plant and marine sources. Among the various derivatives of indoles, Diindolyl methanes have wide medicinal applications such as to induce apoptosis in human cancer cells, antibacterial, Anti-inflammatory, antiviral and hormonal control activities. Therefore, they play essential role in marine as well as terrestrial living systems. In present studies we report novel class of Diindolyl methanes prepared from natural phenolic monoterpenoids, via ortho formylation of phenolic monoterpenoids (Carvacrol, Thymol and Eugenol), followed by synthesis, characterization, anticancer, antioxidant and α-amylase inhibitory activities. All the synthesized derivatives show moderate anticancer activities against human breast cell line MCF7, good antioxidant and α-amylase inhibitory activities using DPPH and α-amylase assay respectively.