Investigations and design of pyridine-2-carboxylic acid thiazol-2-ylamide analogs as methionine aminopeptidase inhibitors using 3D-QSAR and molecular docking

dc.contributor.author Meetei, Potshangbam Angamba
dc.contributor.author Hauser, Alexander S.
dc.contributor.author Raju, Prathigadapa S.
dc.contributor.author Rathore, R. S.
dc.contributor.author Prabhu, N. Prakash
dc.contributor.author Vindal, Vaibhav
dc.date.accessioned 2022-03-27T05:18:23Z
dc.date.available 2022-03-27T05:18:23Z
dc.date.issued 2014-01-01
dc.description.abstract Methionine amino peptidases (MetAPs) are metalloproteases that remove co-translational N-terminal methionine from nascent polypeptide chains. Due to their essential role in protein synthesis, MetAPs are considered as potential targets for antibacterial drugs. In the present work, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on a series of pyridine-2-carboxylic acid thiazol-2-ylamidebased MetAP inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The models were developed using 30 training set molecules. The optimum CoMFA and CoMSIA models obtained for the training set were statistically significant with cross-validated correlation coefficients (q2) of 0.799 and 0.704 and conventional correlation coefficients (r2) of 0.989 and 0.954, respectively. These inhibitors were docked into MetAP active site. The CoMFA and CoMSIA field contour maps correlate well with the structural characteristics of the binding pocket of MetAP active site. Using the knowledge of structure-activity relationship and receptor-ligand interactions from 3D-QSAR model and the docked complexes, four new pyridine-2-carboxylic acid thiazol-2-ylamide analogs were designed. These analogs exhibit significantly better predicted activity than the reported molecules. The present work has implications for the development of novel antibiotics as potent MetAP inhibitors. © Springer Science+Business Media 2014.
dc.identifier.citation Medicinal Chemistry Research. v.23(8)
dc.identifier.issn 10542523
dc.identifier.uri 10.1007/s00044-014-0950-z
dc.identifier.uri http://link.springer.com/10.1007/s00044-014-0950-z
dc.identifier.uri https://dspace.uohyd.ac.in/handle/1/7966
dc.subject 3D-QSAR
dc.subject CoMFA
dc.subject CoMSIA
dc.subject Methionine aminopeptidase inhibitors
dc.subject Molecular docking
dc.subject Pyridine-2-carboxylic acid thiazol-2-ylamide
dc.title Investigations and design of pyridine-2-carboxylic acid thiazol-2-ylamide analogs as methionine aminopeptidase inhibitors using 3D-QSAR and molecular docking
dc.type Journal. Article
dspace.entity.type
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