Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines

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 r(2)(r(r)(pred)) 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.

Synthesis, Crystal Structure, and Fungicidal Activity of a Novel 1,2,3-Thiadiazole Compound

“…10 It is reported that 1,2,3-thiadiazole has beneficial medicinal and agricultural applications. Due to its good bioactivity and usefulness as intermediates in organic synthesis, the chemistry of the 1,2,3-thiadiazole ring has been widely studied.…”

1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story So Far And Perspectives (Part 2): Action in Other Targets and Antitargets

“…Thus, a series of symmetrical and asymmetrical 1,4-DHPs was prepared, bearing a carbamoyl moiety at positions C-3 and C-5 or an aryl ring linked at the N-1 position of the 1,4-DHP scaffold (19). For these compounds the biological activity was evaluated and a 3D-QSAR analysis was carried out [75]. Recently, other imidazolyl-1,4-DHPs (20 and 21) have been reported to have certain antitubercular activity [76,77].…”

Synthesis, Characterization and Docking Studies of Some Novel Dihydropyridine Derivatives

“…[12] antitubercular agents. [13] Dihydropyridine derivatives have gained therapeutic success due to their efficient binding to the active site of the receptors.…”