Molecular Diversity

, Volume 14, Issue 2, pp 285–305

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

  • Atul T. Manvar
  • Raghuvir R. S. Pissurlenkar
  • Vijay R. Virsodia
  • Kuldip D. Upadhyay
  • Dinesh R. Manvar
  • Arun K. Mishra
  • Hrishikesh D. Acharya
  • Alpesh R. Parecha
  • Chintan D. Dholakia
  • Anamik K. Shah
  • Evans C. Coutinho
Full-Length Paper

DOI: 10.1007/s11030-009-9162-8

Cite this article as:
Manvar, A.T., Pissurlenkar, R.R.S., Virsodia, V.R. et al. Mol Divers (2010) 14: 285. doi:10.1007/s11030-009-9162-8

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. tuberculosisH37Rv 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 (r2) of 0.98 and 0.95 with cross-validated r2(q2) 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 \({r^{2} (r^{2}_{\rm pred})}\) 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.

Keywords

1,4-DHPs Antitubercular activity 3D-QSAR CoMFA CoMSIA 

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Atul T. Manvar
    • 1
  • Raghuvir R. S. Pissurlenkar
    • 2
  • Vijay R. Virsodia
    • 3
  • Kuldip D. Upadhyay
    • 4
  • Dinesh R. Manvar
    • 3
  • Arun K. Mishra
    • 3
  • Hrishikesh D. Acharya
    • 3
  • Alpesh R. Parecha
    • 5
  • Chintan D. Dholakia
    • 6
  • Anamik K. Shah
    • 1
  • Evans C. Coutinho
    • 2
  1. 1.Department of ChemistrySaurashtra UniversityRajkotIndia
  2. 2.Department of Pharmaceutical ChemistryBombay College of PharmacyMumbaiIndia
  3. 3.Jubilant OrganosysNoidaIndia
  4. 4.Torrent Research CentreVillage Bhat, GandhinagarIndia
  5. 5.Sun PharmaceuticalsPanoliIndia
  6. 6.Unimark Remedies Ltd.Bavala, AhmedabadIndia