Synthesis of some Novel N-Aryl-1,4-Dihydropyridines Derivatives and Their Biological Evaluation as Potential Antimycobaceterial Agents
Keywords:
1, 4-Dihydropyridines, Antitubercular Activity, Antimycobacterial Activity, Mycobacterium Tuberculosis.Abstract
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 µg/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.
References
- WHO Global Tuberculosis Control Report (2008).
- R. Jain, B. Vaitilingam, A. Nayyar, P.B. Palde, Bioorg. Med. Chem. Lett. 13 (2003) 1051-1054.
- WHO Weekly epidemiological record 78, 15 (2003) 121-128.
- 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.
- E. Miyazaki, M. Miyazaki, J.M. Chan, R.E. Chaissson, W.R. Bishai, Antimicrob. Agents Chemother. 43 (1999) 85-89.
- T. Yoshimatsu, E. Nuermberger, S. Tyagi, R. Chaisson, W. Bishai, J. Grosset, Animicrob. Agents Chemother. 46 (2002) 1875-1879.
- J. Fung-Tomc, B. Minassian, B. Kolek, T. Washo, E. Huczko, D.J. Bonner, Antimicrob. Chemother. 45 (2000) 437-446.
- E.J. Alvirez-Freites, J.L. Carter, M.H. Cynamon, Antimicrob. Agents Chemother. 46 (2002) 1022-1025.
- K. Andries, P. Verhasselt, J.Guillemont, et al. Science 307 (2005) 223-227.
- C.K. Stover, P. Warrener, D.R. VanDevanter, et al. Nature 405 (2000) 962-966.
- M. Matsumoto, H. Hashizume, T. Tomishige, M. Kawasaki, American Society for Microbiology (2005) 204.
- S.K. Arora, N. Sinha, R.K. Sinha, R.S. Uppadhayaya, V.M. Modak, Tilekar, American Society for Microbiology (2004) 212.
- R. Lee, M. Protopopova, E. Crooks, R.A. Slayden, M. Terrot, C.E. Barry III, J Comb. Chem. 5 (2003) 172-187.
- B. Desai, D. Sureja, Y. Naliapara, A. Shah, A. Saxena, Bioorg. Med. Chem. 9 (2001) 1993-1998.
- M.H. Cynamon, S.P. Klemens, T.S. Chou, R.H. Gimi, J.T. Weleh, J. Med. Chem. 35 (1992) 1212-1215.
- 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.
- R.J. Speirs, J.T. Weleh, M.H. Cynamon, Antimicrob. Agents Chemother. 39 (1995) 1269-1271.
- G.A. Wachter, M.C. Davis, A.R. Martin, S.G. Franzblau, J. Med. Chem. 41 (1998) 2436-2438.
- 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.
- O. Prakash, K. Pannu, R. Naithani, H. Kaur, Synth. Commun. 36 (2006) 3479-3485.
- L. Collins, S.G. Franzblau, Antimicrob. Agents Chemother. 41 (2007) 1004-1009.
- 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.
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