Log in

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

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Scheme 1
Fig. 2

Similar content being viewed by others

References

  • 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 

  • 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:2532–2537

    CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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

  • 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 

  • 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 

  • Finegold SM, Garrod L (1995) Bailey and Scott’s diagnostic microbiology, Chap 13, 8th edn. C.V. Mosby, Toronto, pp 171–193

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Jat RK, Jat JL, Pathak DP (2006) Synthesis of benzimidazole derivatives as anti-hypertensive agents. E J Chem 3:278–282

    Article  Google Scholar 

  • 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:1794–1799

    CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Krchnak V, Holladay MW (2002) Solid phase heterocyclic chemistry. Chem Rev 102:61–92. doi:10.1021/cr010123h

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Lazer ES, Matteo MR, Possanza GJ (1987) Benzimidazole derivatives with a typical antiinflammatory activity. J Med Chem 30:726–729. doi:10.1021/jm00387a026

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Nfzi A, Ostresh JM, Houghten RA (1997) The current status of heterocyclic combinatorial libraries. Chem Rev 97:449–472. doi:10.1021/cr960010b

    Article  Google Scholar 

  • Olkkola KT, Brunetto AV, Mattila MJ (1994) Pharmacokinetics of oxicam nonsteroidal anti-inflammatory agents. Clin Pharmacokinet 26:107–120

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • **ao 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

    Article  PubMed  CAS  Google Scholar 

  • 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 49:843–848

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful to the Head, Department of Chemistry, Mahatma Gandhi Campus, Bhavnagar University, Bhavnagar for providing laboratory facilities.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. C. Desai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Desai, N.C., Pandya, D.D., Joshi, V.V. et al. Synthesis, characterization and antimicrobial screening of hybrid molecules containing benzimidazole-pyrazole and pyridine nucleus. Med Chem Res 21, 4463–4472 (2012). https://doi.org/10.1007/s00044-012-9990-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-012-9990-4

Keywords

Navigation