Journal ArticleDOI
Insights on inhibition of Plasmodium falciparum plasmepsin I by novel epoxyazadiradione derivatives - molecular docking and comparative molecular field analysis.
Mahalakshmi Thillainayagam,Kullappan Malathi,Anand Anbarasu,Harpreet Singh,Renu Bahadur,Sudha Ramaiah +5 more
Reads0
Chats0
TLDR
The Surflex dock analysis of 41 compounds against an indispensable target, plasmepsin I (PM-I) revealed that around 70% of the compounds are found to have good binding capacity with the consensus score (C-score) of 5 to 4 with few hydrogen bonds.Abstract:
In the present study, we have explored the anti-malarial potential of epoxyazadiradione, the natural entity extracted from the neem seed oil and its chemical derivatives, against Plasmodium falciparum. The Surflex dock analysis of 41 compounds against an indispensable target, plasmepsin I (PM-I) revealed that around 70% of the compounds are found to have good binding capacity with the consensus score (C-score) of 5 to 4 with few hydrogen bonds. To elucidate the major structural requirements, vital for binding with the plasmepsin enzyme and to develop the predictive models, three-dimentional quantitative structural activity relationship (3D-QSAR) - comparative molecular field analysis (CoMFA) was carried out using Sybyl X.0. Robust and predictive models were obtained with cross-validated correlation coefficient (q2) value of 0.967 and the non-cross-validated correlation coefficient (r2) value of 0.825, which were validated by an external test set with the predictive correlation coefficient r2(pred) values of 0.773. Three zones were identified for substitution with bulky groups and one zone for substitution with non-bulky groups. Three positions favouring the electronegative group substitution and one for the electropositive group substitution were identified. The physicochemical properties of ligands with the highest C-score were studied. Communicated by Ramaswamy H. Sarma.read more
Citations
More filters
Journal ArticleDOI
In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19.
Seshu Vardhan,Suban K. Sahoo +1 more
TL;DR: The protein-ligand interaction study revealed that these phytochemicals bind with the amino acid residues at the active site of the target proteins of SARS-CoV-2, therefore, the core structure of these potential hits can be used for further lead optimization to design drugs for Sars-Cov-2.
Journal ArticleDOI
Intervening Effects of Total Alkaloids of Corydalis saxicola Bunting on Rats With Antibiotic-Induced Gut Microbiota Dysbiosis Based on 16S rRNA Gene Sequencing and Untargeted Metabolomics Analyses
Xi Liu,Hua Zheng,Rigang Lu,Huimin Huang,Hongjia Zhu,Chunli Yin,Yi-Yi Mo,Jinxia Wu,Xuwen Liu,Ming Deng,Danfeng Li,Bang Cheng,Fang Wu,Fang Wu,Yonghong Liang,Hongwei Guo,Hui Song,Zhiheng Su +17 more
TL;DR: This study provides a comprehensive overview of the intervening effects of TACS on the host metabolic phenotype and gut microbiome in rats with gut microbiota dysbiosis, and it presents new insights for the discovery of effective drugs and the best therapeutic approaches.
Journal ArticleDOI
VDA-RWLRLS: An anti-SARS-CoV-2 drug prioritizing framework combining an unbalanced bi-random walk and Laplacian regularized least squares
Abbo Junker,Maximilian Berbig +1 more
TL;DR: Wang et al. as mentioned in this paper developed a Virus-Drug Association (VDA) identification framework combining unbalanced bi-Random Walk, Laplacian Regularized Least Squares, molecular docking, and molecular dynamics simulation to find clues for the treatment of COVID-19.
Journal ArticleDOI
Identification of potential inhibitors for Klebsiella pneumoniae carbapenemase-3: a molecular docking and dynamics study.
TL;DR: This study provides a clear understanding of the mechanism of drug resistance and provides valuable inputs for the development of inhibitors against KPC-3 expressing K. pneumoniae strains.
Journal ArticleDOI
Identification of bioactive natural compounds as efficient inhibitors against Mycobacterium tuberculosis protein-targets: A molecular docking and molecular dynamics simulation study
Sravan Kumar Miryala,Soumya Basu,Aniket Naha,Reetika Debroy,Sudha Ramaiah,Anand Anbarasu,Saravanan Natarajan +6 more
TL;DR: Glycyrrhizin, Laccaic acid and Swertiamarin could be developed as multi-target specific alternative drug candidates and could be subjected to experimental validations against MDR/XDR Mtb.
References
More filters
Journal ArticleDOI
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules
TL;DR: The new SwissADME web tool is presented that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar are presented.
Journal ArticleDOI
Molecular properties that influence the oral bioavailability of drug candidates.
Daniel F. Veber,Stephen R. Johnson,Hung-Yuan Cheng,Brian R. Smith,Keith W. Ward,Kenneth D. Kopple +5 more
TL;DR: Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count are found to be important predictors of good oral bioavailability, independent of molecular weight.
Journal ArticleDOI
Validation of the general purpose Tripos 5.2 force field
TL;DR: In this paper, a molecular mechanics force field implemented in the Sybyl program is described along with a statistical evaluation of its efficiency on a variety of compounds by analysis of internal coordinates and thermodynamic barriers.
Journal ArticleDOI
A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases.
TL;DR: The effective range of physicochemical properties presented here can be used in the design of drug-like combinatorial libraries as well as in developing a more efficient corporate medicinal chemistry library.
Related Papers (5)
3D-QSAR analysis of cycloguanil derivatives as inhibitors of A16V + S108T mutant Plasmodium falciparum dihydrofolate reductase enzyme.
Legesse Adane,Prasad V. Bharatam +1 more
Drug discovery studies on quinoline-based derivatives as potential antimalarial agents.
Molecular modeling studies of dihydro-alkyloxy-benzyl-oxopyrimidines (DABOs) as non-nucleoside inhibitors of HIV-1 reverse transcriptase using 3D-QSAR, Topomer CoMFA and molecular docking simulations
Ming-Hui Dong,Yu-Jie Ren +1 more