Synthesis of some Novel N-Aryl-1,4-Dihydropyridines Derivatives and Their Biological Evaluation as Potential Antimycobaceterial Agents

Authors(1) :-Amish P. Khamar

Tuberculosis, due to its unyielding nature, is now a chief civic health threat. The associated renaissance of TB with the MDR or XDR-TB and HIV/AIDS epidemic has exposed the infirmities of the current drug armatorium. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant antitubercular activity. We have synthesized new N-aryl-1,4-dihydropyridines bearing carbethoxy and acetyl group at C-3 and C-5 of the DHP ring. In addition, 1H-pyrazole ring is substitutes at C-4 position. The in vitro antitubercular activity of compounds against Mycobacterium tuberculosis H37Rv was evaluated. The lowest minimum inhibitory concentration value, 0.02 g/mL, was found for diethyl 1-(2-chlorophenyl)-1,4-dihydro-2,6-dimethyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine-3,5-dicarboxylate 4e making it more potent than first line antitubercular drug isoniazid. In addition, this compound exhibited relatively low cytotoxicity.

Authors and Affiliations

Amish P. Khamar
Arts, Science & R. A. Patel Commerce College, Bhadran, Gujarat, India

1, 4-Dihydropyridines, Antitubercular Activity, Antimycobacterial Activity, Mycobacterium Tuberculosis.

  1. WHO Global Tuberculosis Control Report (2008).
  2. R. Jain, B. Vaitilingam, A. Nayyar, P.B. Palde, Bioorg. Med. Chem. Lett. 13 (2003) 1051-1054.
  3. WHO Weekly epidemiological record 78, 15 (2003) 121-128.
  4. M. Zignol, M.S. Hosseini, A. Wright, C.L. Weezenbeek, P. Nunn, C.J. Watt, C.G. Williams, C.J. Dye, Infect. Dis. 194 (2006) 479-485.
  5. E. Miyazaki, M. Miyazaki, J.M. Chan, R.E. Chaissson, W.R. Bishai, Antimicrob. Agents Chemother. 43 (1999) 85-89.
  6. T. Yoshimatsu, E. Nuermberger, S. Tyagi, R. Chaisson, W. Bishai, J. Grosset, Animicrob. Agents Chemother. 46 (2002) 1875-1879.
  7. J. Fung-Tomc, B. Minassian, B. Kolek, T. Washo, E. Huczko, D.J. Bonner, Antimicrob. Chemother. 45 (2000) 437-446.
  8. E.J. Alvirez-Freites, J.L. Carter, M.H. Cynamon, Antimicrob. Agents Chemother. 46 (2002) 1022-1025.
  9. K. Andries, P. Verhasselt, J.Guillemont, et al. Science 307 (2005) 223-227.
  10. C.K. Stover, P. Warrener, D.R. VanDevanter, et al. Nature 405 (2000) 962-966.
  11. M. Matsumoto, H. Hashizume, T. Tomishige, M. Kawasaki, American Society for Microbiology (2005) 204.
  12. S.K. Arora, N. Sinha, R.K. Sinha, R.S. Uppadhayaya, V.M. Modak, Tilekar, American Society for Microbiology (2004) 212.
  13. R. Lee, M. Protopopova, E. Crooks, R.A. Slayden, M. Terrot, C.E. Barry III, J Comb. Chem. 5 (2003) 172-187.
  14. B. Desai, D. Sureja, Y. Naliapara, A. Shah, A. Saxena, Bioorg. Med. Chem. 9 (2001) 1993-1998.
  15. M.H. Cynamon, S.P. Klemens, T.S. Chou, R.H. Gimi, J.T. Weleh, J. Med. Chem. 35 (1992) 1212-1215.
  16. M.H. Cynamon, R.H. Gimi, F. Gyenes, C.A. Sharpe, K.E. Bergmann, H.J. Jan, L.B. Gregor, R. Rapolu, G. Luciano, J.T. Weleh, J. Med. Chem. 38 (1995) 3902-3907.
  17. R.J. Speirs, J.T. Weleh, M.H. Cynamon, Antimicrob. Agents Chemother. 39 (1995) 1269-1271.
  18. G.A. Wachter, M.C. Davis, A.R. Martin, S.G. Franzblau, J. Med. Chem. 41 (1998) 2436-2438.
  19. D. Castagnolo, F. Manetti, M. Radi, B. Bechi, M. Pagano, A. De Logu, R. Meleddu, M. Saddi, M. Botta, Bioorg. Med. Chem. 17 (2009) 5716–5721.
  20. O. Prakash, K. Pannu, R. Naithani, H. Kaur, Synth. Commun. 36 (2006) 3479-3485.
  21. L. Collins, S.G. Franzblau, Antimicrob. Agents Chemother. 41 (2007) 1004-1009.
  22. I. Orme, J. Secrist, S. Anathan, C. Kwong, J. maddry, R. Reynolds, A. Poffenberger, M. Michael, L. Moller, J. Krahenbuh, L. Adams, A. Biswas, S. Franzblau, D. Rouse, D. Winfield, J. Brooks, Antimicrob. Agents Chemother. 45 (2001) 1943-1946.

Publication Details

Published in : Volume 1 | Issue 1 | 2014
Date of Publication : 2014-12-30
License:  This work is licensed under a Creative Commons Attribution 4.0 International License.
Page(s) : 174-182
Manuscript Number : IJSRSET184102
Publisher : Technoscience Academy

Print ISSN : 2395-1990, Online ISSN : 2394-4099

Cite This Article :

Amish P. Khamar, " Synthesis of some Novel N-Aryl-1,4-Dihydropyridines Derivatives and Their Biological Evaluation as Potential Antimycobaceterial Agents, International Journal of Scientific Research in Science, Engineering and Technology(IJSRSET), Print ISSN : 2395-1990, Online ISSN : 2394-4099, Volume 1, Issue 1, pp.174-182, -2014.
Journal URL : http://ijsrset.com/IJSRSET184102

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