In vitro Anti-tubercular Screening of Newly Synthesized Benzimidazole Derivatives
A series of 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)-2-propen-1-one were allowed to react with hydrazine hydrate and phenyl hydrazine in submitted reactions to get pyrazoline and phenyl pyrazoline derivatives. All the compounds entered for screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv strain (ATCC 27294) using Microplate Alamar Blue Assay (MABA) susceptibility test. The results expressed as MIC (minimum inhibitory concentration) in μg/mL. Among the fifteen compounds, eight compounds were found to have MIC values less than 10 μg/mL. These were subjected for cytotoxicity assay in VERO cells to determine CC50 (cytotoxic concentration 50%) values and finally SI (Selectivity Index) were calculated. Compound (XV) 2-[5-(4- fluorophenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-1Hbenzimidazole was considered the best candidate of the series that could be a good starting point to develop new lead compounds in the fight against tuberculosis.
[1] Brenwald, N.P., Gill, M.J., and Wise, R .(1998) Prevalence of a putative
efflux mechanism among fluoroquinolone -resistant clinical isolates of
streptococcus pneumoniae.Antimiarob.Agents.Chemother 42,2032-
2035.
[2] Klemens,S.P., De Stefano,M.S., and Cynamon,M.H (1993.Therapy of
multidrug resistant tuberculosis:lessons from studies with mice.
Antimiarob.Agents.Chemother 37, 2344-2347.
[3] Corbett,E.L., Watt,C.J., Walker,N.,Maher,D., Williams,B.G.,
Raviglione,M.C., and Dye,C.(2003) The growing burdens of
tuberculosis:global trends and interactions with HIV epidemic. Arch
Intern Med 163,1009-1021
[4] Aridoss, G., Amirthaganesan, S., Kumar, N.A., Kim, J.T., Lim, K.T.,
Kabilan, S., Jeong, Y.T. A facile synthesis, antibacterial, and
antitubercular studies of some piperidin-4-one and tetrahydropyridine derivatives. Bioorg Med Chem Lett. 2008, 18(24):6542-8. Epub 2008
Oct 14.
[5] Gill, C., Jadhav, G., Shaikh, M., Kale, R., Ghawalkar, A., Nagargoje, D.,
Shiradkar. Clubbed (1, 2, 3) triazoles by fluorine benzimidazole: a novel
approach to H37Rv inhibitors as a potential treatment for tuberculosis
M. Bioorg Med Chem Lett. 2008, 18(23):6244-7. Epub
2008 Oct 2
[6] Mohamed, B.G., Hussein, M.A., Abdel-Alim, A.A., Hashem, M.
Synthesis and antimicrobial activity of some new 1-alkyl-2-alkylthio-1,
2, 4-triazolobenzimidazole derivatives. Arch Pharm Res. 2006,
29(1):26-33.
[7] Gasparová, R., Lácová, M., el-Shaaer, H.M., Odlerová, Z. Synthesis and
antimycobacterial activity of some new 3-heterocyclic substituted
chromones. Farmaco. 1997, 52(4):251-3.
[8] Geban, O., Ertepinar, H., Ozden, S. QSAR analysis of a set of
benzimidazole derivatives based on their tuberculostatic activities.
Pharmazie. 1996, 51(1):34-6.
[9] Alunni Bistocchi, G., De Meo, G., Pedini, M., Ricci, A., Bastianini, L.,
Sposini, T., Sbaraglia, G., Jacquignon, P. (New heterocyclic derivatives
of benzimidazole with germicidal activity. III. Synthesis and activity of
derivatives of (formyl-5'-furyl-2')-2-benzimidazole with different
substitutions at position 5). Farmaco (Sci). 1986 41(12):970-83.
[10] Bell, S.C., Wei, P.H. Syntheses of heterocylic fused thiazole acetic
acids. 2. Bell SC, Wei PH. J Med Chem. 1976, 19(4):524-30.
[11] Sawlewicz J, Milczarska B, Manowska W. Reactions of
cyanomethylbenzimidazoles. Part II. Reaction of
cyanomethylbenzimidazoles with aldehydes methylketones and nitroso
compounds. Pol J Pharmacol Pharm. 1975, 27(2):187-201.
[12] Synthesis, structure activity relationship and anti-tubercular activity of
novel pyrazoline derivatives. M.A. Ali, M. Shaharyar, A. A.
Siddiqui, Eur. J. Med. Chem. 42 (2007) 268-275.
[13] Synthesis and in vitro antimycobacterial activity of N1-nicotinoyl-3-(4--
hydroxy-3--methyl phenyl)-5-((sub)phenyl)-2-pyrazoline. M. Shaharyar,
A.A.Siddiqui, M.A. Ali, D. Shriram, P.Yogeeshwari, Bioorg. Med.
Chem. Lett.16 (2006) 3947-3949.
[14] G.W.H. Cheeseman, J. Chem. Soc. (1964) 4645-46.
[15] Collins, L. and Franzblau, S. G. (1997) Microplate alamar blue assay
versus BACTEC 460 system for high-throughput screening of
compounds against Mycobacterium tuberculosis and Mycobacterium
avium. Antimicrob. Agents Chemother., 41, 1004-1009.
[1] Brenwald, N.P., Gill, M.J., and Wise, R .(1998) Prevalence of a putative
efflux mechanism among fluoroquinolone -resistant clinical isolates of
streptococcus pneumoniae.Antimiarob.Agents.Chemother 42,2032-
2035.
[2] Klemens,S.P., De Stefano,M.S., and Cynamon,M.H (1993.Therapy of
multidrug resistant tuberculosis:lessons from studies with mice.
Antimiarob.Agents.Chemother 37, 2344-2347.
[3] Corbett,E.L., Watt,C.J., Walker,N.,Maher,D., Williams,B.G.,
Raviglione,M.C., and Dye,C.(2003) The growing burdens of
tuberculosis:global trends and interactions with HIV epidemic. Arch
Intern Med 163,1009-1021
[4] Aridoss, G., Amirthaganesan, S., Kumar, N.A., Kim, J.T., Lim, K.T.,
Kabilan, S., Jeong, Y.T. A facile synthesis, antibacterial, and
antitubercular studies of some piperidin-4-one and tetrahydropyridine derivatives. Bioorg Med Chem Lett. 2008, 18(24):6542-8. Epub 2008
Oct 14.
[5] Gill, C., Jadhav, G., Shaikh, M., Kale, R., Ghawalkar, A., Nagargoje, D.,
Shiradkar. Clubbed (1, 2, 3) triazoles by fluorine benzimidazole: a novel
approach to H37Rv inhibitors as a potential treatment for tuberculosis
M. Bioorg Med Chem Lett. 2008, 18(23):6244-7. Epub
2008 Oct 2
[6] Mohamed, B.G., Hussein, M.A., Abdel-Alim, A.A., Hashem, M.
Synthesis and antimicrobial activity of some new 1-alkyl-2-alkylthio-1,
2, 4-triazolobenzimidazole derivatives. Arch Pharm Res. 2006,
29(1):26-33.
[7] Gasparová, R., Lácová, M., el-Shaaer, H.M., Odlerová, Z. Synthesis and
antimycobacterial activity of some new 3-heterocyclic substituted
chromones. Farmaco. 1997, 52(4):251-3.
[8] Geban, O., Ertepinar, H., Ozden, S. QSAR analysis of a set of
benzimidazole derivatives based on their tuberculostatic activities.
Pharmazie. 1996, 51(1):34-6.
[9] Alunni Bistocchi, G., De Meo, G., Pedini, M., Ricci, A., Bastianini, L.,
Sposini, T., Sbaraglia, G., Jacquignon, P. (New heterocyclic derivatives
of benzimidazole with germicidal activity. III. Synthesis and activity of
derivatives of (formyl-5'-furyl-2')-2-benzimidazole with different
substitutions at position 5). Farmaco (Sci). 1986 41(12):970-83.
[10] Bell, S.C., Wei, P.H. Syntheses of heterocylic fused thiazole acetic
acids. 2. Bell SC, Wei PH. J Med Chem. 1976, 19(4):524-30.
[11] Sawlewicz J, Milczarska B, Manowska W. Reactions of
cyanomethylbenzimidazoles. Part II. Reaction of
cyanomethylbenzimidazoles with aldehydes methylketones and nitroso
compounds. Pol J Pharmacol Pharm. 1975, 27(2):187-201.
[12] Synthesis, structure activity relationship and anti-tubercular activity of
novel pyrazoline derivatives. M.A. Ali, M. Shaharyar, A. A.
Siddiqui, Eur. J. Med. Chem. 42 (2007) 268-275.
[13] Synthesis and in vitro antimycobacterial activity of N1-nicotinoyl-3-(4--
hydroxy-3--methyl phenyl)-5-((sub)phenyl)-2-pyrazoline. M. Shaharyar,
A.A.Siddiqui, M.A. Ali, D. Shriram, P.Yogeeshwari, Bioorg. Med.
Chem. Lett.16 (2006) 3947-3949.
[14] G.W.H. Cheeseman, J. Chem. Soc. (1964) 4645-46.
[15] Collins, L. and Franzblau, S. G. (1997) Microplate alamar blue assay
versus BACTEC 460 system for high-throughput screening of
compounds against Mycobacterium tuberculosis and Mycobacterium
avium. Antimicrob. Agents Chemother., 41, 1004-1009.
@article{"International Journal of Medical, Medicine and Health Sciences:53347", author = "M. Shahar Yar and M. Mustaqeem Abdullah and Jaseela Majeed", title = "In vitro Anti-tubercular Screening of Newly Synthesized Benzimidazole Derivatives", abstract = "A series of 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)-2-propen-1-one were allowed to react with hydrazine hydrate and phenyl hydrazine in submitted reactions to get pyrazoline and phenyl pyrazoline derivatives. All the compounds entered for screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv strain (ATCC 27294) using Microplate Alamar Blue Assay (MABA) susceptibility test. The results expressed as MIC (minimum inhibitory concentration) in μg/mL. Among the fifteen compounds, eight compounds were found to have MIC values less than 10 μg/mL. These were subjected for cytotoxicity assay in VERO cells to determine CC50 (cytotoxic concentration 50%) values and finally SI (Selectivity Index) were calculated. Compound (XV) 2-[5-(4- fluorophenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-1Hbenzimidazole was considered the best candidate of the series that could be a good starting point to develop new lead compounds in the fight against tuberculosis.
", keywords = "anti-tubercular activity, benzimidazole, pyrazoline.", volume = "3", number = "7", pages = "127-7", }
