Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines. Molecular diversity [Mol Divers] Journal article | | Title | Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines. | | Author(s) | Manvar AT, Pissurlenkar RR, Virsodia VR, Upadhyay KD, Manvar DR, Mishra AK, Acharya HD, Parecha AR, Dholakia CD, Shah AK, Coutinho EC | | Institution | Department of Chemistry, Saurashtra University, Rajkot, 360 005, Gujarat, India. | | Source | Mol Divers 2009 Jun 24. | | Abstract | In continuation of our research program on new antitubercular agents, this article is a report of the synthesis of 97 various symmetrical, unsymmetrical, and N-substituted 1,4-dihydropyridines. The synthesized molecules were tested for their activity against M. tuberculosis H (37)Rv strain with rifampin as the standard drug. The percentage inhibition was found in the range 3-93%. In an effort to understand the relationship between structure and activity, 3D-QSAR studies were also carried out on a subset that is representative of the molecules synthesized. For the generation of the QSAR models, a training set of 35 diverse molecules representing the synthesized molecules was utilized. The molecules were aligned using the atom-fit technique. The CoMFA and CoMSIA models generated on the molecules aligned by the atom-fit method show a correlation coefficient (r (2)) of 0.98 and 0.95 with cross-validated r (2)(q (2)) of 0.56 and 0.62, respectively. The 3D-QSAR models were externally validated against a test set of 19 molecules (aligned previously with the training set) for which the predictive [Formula: see text] is recorded as 0.74 and 0.69 for the CoMFA and CoMSIA models, respectively. The models were checked for chance correlation through y-scrambling. The QSAR models revealed the importance of the conformational flexibility of the substituents in antitubercular activity. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19554465 |
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