Medicinal Chemistry Research

, Volume 21, Issue 12, pp 4463–4472 | Cite as

Synthesis, characterization and antimicrobial screening of hybrid molecules containing benzimidazole-pyrazole and pyridine nucleus

  • N. C. Desai
  • D. D. Pandya
  • V. V. Joshi
  • K. M. Rajpara
  • H. V. Vaghani
  • H. M. Satodiya
Original Research

Abstract

The rising prevalence of multi-drug resistant Gram-positive, Gram-negative bacteria and fungi continues to provide momentum for search and development of novel active antimicrobial agents against these pathogens. In continuation to this, the present article deals with the synthesis and antimicrobial activity of a novel series of (3-(1H-benzo[d]imidazol-2-yl)-5-(aryl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones 4an, synthesized by the reaction of benzimidazolyl chalcones with isoniazide 3. The structures of synthesized compounds were elucidated on the basis of IR, NMR, and mass spectra. The newly synthesized compounds 4an were screened for their antimicrobial activity against different strains of bacteria and fungi using serial broth dilution method. Compounds 4d, 4f, 4h, and 4g were found to be most active with MIC of 25 μg/mL against selected bacterial strains. Compounds 4c, 4g, and 4n were found to be most active with MIC of 100 μg/mL against selected fungal strains.

Keywords

Benzimidazole-pyrazole Pyridine Antibacterial screening Antifungal screening MIC 

References

  1. Al-Bayati FA, Al-Mola HF (2008) Antibacterial and antifungal activities of different parts of Tribulus terrestris L. growing in Iraq. J Zhenjiang 9:154–159. doi:10.1631/jzus.B0720251 Google Scholar
  2. Amir M, Kumar S (2005) Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of 3,5-dimethyl pyrazoles, 3-methyl pyrazol-5-ones and 3,5-disubstituted pyrazolines. Indian J Chem 44B:2532–2537Google Scholar
  3. Beaulieu PL, Bousquet Y, Gauthier J, Gillard J, Marquis M, McKercher G, Pellerin C, Valois S, Kukolj G (2004) Non-nucleoside benzimidazole-based allosteric inhibitors of the hepatitis C virus NS5B polymerase: inhibition of subgenomic hepatitis C virus RNA replicons in Huh-7 cells. J Med Chem 47:6884–6892. doi:10.1021/jm040134d PubMedCrossRefGoogle Scholar
  4. Bekhit AA, Ashour HMA, Guemei AA (2005) Novel pyrazole derivatives as potential promising anti-inflammatory antimicrobial agents. Arch Pharm 338:167–174. doi:10.1002/ardp.200400940 CrossRefGoogle Scholar
  5. Bringmann G, Reichert Y, Kane VV (2004) The total synthesis of streptonigrin and related antitumor antibiotic natural products. Tetrahedron 60:3539–3574. doi:10.1016/j.tet.2004.02.060 CrossRefGoogle Scholar
  6. Desai NC, Dodiya AM, Kumar M, Bhatt N (2010a) Dimeric 2-(2-chlorophenyl)-quinazolin-4-ones as potential antimicrobial agents. Med Chem Res. doi:10.1007/s00044-011-9621-5 Google Scholar
  7. Desai NC, Chhabria MT, Dodiya AM, Bhavsar AM (2010b) Synthesis, characterization, anticancer activity, and QSAR-studies of some new tetrahydropyrimidines. Med Chem Res. doi:10.1007/s00044-010-9481-4 Google Scholar
  8. Desai NC, Dodiya AM, Makwana AH (2011a) Antimicrobial screening of novel synthesized benzimidazole nucleus containing 4-oxo-thiazolidine derivatives. Med Chem Res. doi:10.1007/s00044-011-9752-8 Google Scholar
  9. Desai NC, Dodiya AM, Shihora PN (2011b) A clubbed quinazolinone and 4-thiazolidinone as potential antimicrobial agents. Med Chem Res. doi:10.1007/s00044-011-9674-5 Google Scholar
  10. Desai NC, Maheta AS, Rajpara KM, Joshi VV, Vaghani HV, Satodiya HM (2011c) Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity. J Saudi Chem Soc. doi:10.1016/j.jscs.2011.11.021
  11. Desai NC, Dodiya AM, Shihory NR (2011d) A search of novel antimicrobial based on benzimidazole and 2-pyridone heterocycles. Med Chem Res. doi:10.1007/s00044-011-9782-2 Google Scholar
  12. Desai NC, Dodiya A, Rajpara KM, Rupala YM (2011e) Synthesis and antimicrobial screening of 1,3,4-oxadiazole and clubbed thiophene derivatives. J Saudi Chem Soc. doi:10.1016/j.jscs.2011.06.020 Google Scholar
  13. Finegold SM, Garrod L (1995) Bailey and Scott’s diagnostic microbiology, Chap 13, 8th edn. C.V. Mosby, Toronto, pp 171–193Google Scholar
  14. Garuti L, Roberti M, Malagoli M, Rossi T, Castelli M (2000) Synthesis and antiproliferative activity of some benzimidazole-4,7-dione derivatives. Bioorg Med Chem Lett 10:2193–2195. doi:10.1016/S0960-894X(00)00429-7 PubMedCrossRefGoogle Scholar
  15. Gatta L, Perna F, Figura N, Ricci C, Holton J, D’Anna L, Miglioli M, Vaira D (2003) Antimicrobial activity of esomeprazole versus omperazole against Helicobacter pylori. J Antimicrob Chemother 51:439–442. doi:10.1093/jac/dkg085 PubMedCrossRefGoogle Scholar
  16. Goker H, Kus C, Boykin DW, Yildiz S, Altanlar N (2002) Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against Candida species. Bioorg Med Chem 10:2589–2596. doi:10.1016/S0968-0896(02)00103-7 PubMedCrossRefGoogle Scholar
  17. Jat RK, Jat JL, Pathak DP (2006) Synthesis of benzimidazole derivatives as anti-hypertensive agents. E J Chem 3:278–282CrossRefGoogle Scholar
  18. Kalirajan R, Rathore L, Jubie S, Gowramma B, Gomathy S, Sankar S (2011) Microwave assisted synthesis of some novel pyrazole substituted benzimidazole and evaluation of their biological activity. Indian J Chem 50B:1794–1799Google Scholar
  19. Kees KL, Fitzgerald JJ Jr, Steiner KE, Mattes JF, Mihan B, Tosi T, Mondoro D, McCaleb ML (1996) New potent antihyperglycemic agents in db/db mice: synthesis and structure-activity relationship studies of (4-substitutedbenzyl)(trifluoromethyl) pyrazoles and –pyrazolones. J Med Chem 39:3920–3928. doi:10.1021/jm960444z PubMedCrossRefGoogle Scholar
  20. Krchnak V, Holladay MW (2002) Solid phase heterocyclic chemistry. Chem Rev 102:61–92. doi:10.1021/cr010123h PubMedCrossRefGoogle Scholar
  21. Kus C, Ayhan-Kilcigil G, Can Eke B, Iscan M (2004) Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver. Arch Pharm Res 27:156–163. doi:10.1007/BF02980099 PubMedCrossRefGoogle Scholar
  22. Lazer ES, Matteo MR, Possanza GJ (1987) Benzimidazole derivatives with a typical antiinflammatory activity. J Med Chem 30:726–729. doi:10.1021/jm00387a026 PubMedCrossRefGoogle Scholar
  23. Mavrova AT, Denkova PS, Tsenov YA, Anichina KK, Vutchev DL (2007) Synthesis and antitrichinellosis activity of some bis(benzimidazol-2-yl)amines. Bioorg Med Chem 15:6291–6297. doi:10.1016/j.bmc.2007.06.017 PubMedCrossRefGoogle Scholar
  24. Navarette-Vazquez G, Cedillo R, Hernandez-Campos A, Yepez L, Hernandez-Luis F, Valdez J, Morales R, Cortes R, Hernandez M, Castillo R (2001) Synthesis and antiparasitic activity of 2-(trifluoromethyl)benzimidazole derivatives. Bioorg Med Chem Lett 11:187–190. doi:10.1016/S0960-894X(00)00619-3 CrossRefGoogle Scholar
  25. Nfzi A, Ostresh JM, Houghten RA (1997) The current status of heterocyclic combinatorial libraries. Chem Rev 97:449–472. doi:10.1021/cr960010b CrossRefGoogle Scholar
  26. Olkkola KT, Brunetto AV, Mattila MJ (1994) Pharmacokinetics of oxicam nonsteroidal anti-inflammatory agents. Clin Pharmacokinet 26:107–120PubMedCrossRefGoogle Scholar
  27. Ouattara M, Sissouma D, Kone MW, Menan HE, Toure SA, Ouattara L (2011) Synthesis and anthelmintic activity of some hybrid Benzimidazolyl-chalcone derivatives. Trop J Pharm Res 10:767–775. doi:org/10.4314/tjpr.v10i6.10 CrossRefGoogle Scholar
  28. Pagano MA, Andrzejewska M, Ruzzene M, Sarno S, Cesaro L, Bain J, Elliott M, Meggio F, Kazimierczuk Z, Pinna LA (2004) Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem 47:6239–6247. doi:10.1021/jm049854a PubMedCrossRefGoogle Scholar
  29. Rao A, Chimirri A, De Clercq E, Monforte AM, Monforte P, Pannecouque C, Zappalà M (2002) Synthesis and anti-hIV activity of 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole structurally-related 1,2-substituted benzimidazoles. Farmaco 57:819–823. doi:10.1016/S0014-827X(02)01300-9 PubMedCrossRefGoogle Scholar
  30. Refaat HM (2010) Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur J Med Chem 45:2949–2956. doi:10.1016/j.ejmech.2010.03.022 PubMedCrossRefGoogle Scholar
  31. Shaharyar M, Abdullah MM, Bakht MA, Majeed J (2010) Pyrazoline bearing benzimidazoles: search for anticancer agent. Eur J Med Chem 45:114–119. doi:10.1016/j.ejmech.2009.09.032 PubMedCrossRefGoogle Scholar
  32. Starcevic K, Kralj M, Ester K, Sabol I, Grace M, Pavelic K, Karminski-Zamola G (2007) Synthesis, antiviral and antitumor activity of 2-substituted-5-amidino-benzimidazoles. Bioorg Med Chem 15:4419–4423. doi:10.1016/j.bmc.2007.04.032 PubMedCrossRefGoogle Scholar
  33. Taylor BM, Crittenden NJ, Bruden MN, Wishka DG, Morris J, Richards IM, Sun FF (1991) Biological activity of leukotriene B4 analogs: inhibition of guinea pig eosinophil migration in vitro by the 2,6-disubstituted pyridine analogs U-75,302 and U-75,485. Prostaglandins 42:211–224. doi:10.1016/0090-6980(91)90111-R PubMedCrossRefGoogle Scholar
  34. Terrett NK, Gardner M, Gordon DW, Kobeylecki RJ, Steele J (1995) Combinatorial synthesis–the design of compound libraries and their application to drug discovery. Tetrahedron 51:8135–8173. doi:10.1016/0040-4020(95)00467-M CrossRefGoogle Scholar
  35. Ueno H, Katoh S, Yokota K, Hoshi J-I, Hayashi M, Uchida I, Aisaka K, Hase Y, Cho H (2004) Structure-activity relationships of potent and selective factor Xa inhibitors: benzimidazole derivatives with the side chain oriented to the prime site of factor Xa. Bioorg Med Chem Lett 14:4281–4286. doi:10.1016/j.bmcl.2004.05.092 PubMedCrossRefGoogle Scholar
  36. Xiao L, Saeed K, Herd RP (1996) Efficacy of albendazole and fenbedazole against Giardia infection in cattle. Vet Parasitol 61:165–170. doi:10.1016/0304-4017(95)00802-0 PubMedCrossRefGoogle Scholar
  37. Zelenin KN, Bezhan IP, Pastushenkov LV, Gromova EG, Lesiovskaja EE, Chakchir BA, Melnikova LF (1999) Anti-inflammatory activity of 2-acyl-5(3)-hydroxytetrahydro-1H-pyrazole derivatives. Arzneimittelforschung 49:843–848PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • N. C. Desai
    • 1
  • D. D. Pandya
    • 1
  • V. V. Joshi
    • 1
  • K. M. Rajpara
    • 1
  • H. V. Vaghani
    • 1
  • H. M. Satodiya
    • 1
  1. 1.Division of Medicinal Chemistry, Department of ChemistryMahatma Gandhi Campus, Bhavnagar UniversityBhavnagarIndia

Personalised recommendations