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Diverse Pharmacological aspects of Benzimidazole Derivatives: A Review

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Author Affiliations

  • 1 Dept. of Chemistry & Post Graduate Research Centre, Abeda Inamdar Sr. College of Arts, Science & Commerce, Camp, Pune – 411001, INDIA

Res.J.chem.sci., Volume 4, Issue (4), Pages 78-88, April,18 (2014)

Abstract

Benzimidazole is the heterocyclic compound formed by the fusion of benzene and imidazole ring. Benzimidazole analogs are of great significant because of their various clinical applications and biological activity. Benzimidazoles are considered as an optimistic class of bioactive heterocyclic compounds that possesses a range of biological activities. The work in this article relates to benzimidazole as it is a versatile heterocycle possessing a wide spectrum of biological activities like antimicrobial, antiviral, antidiabetic, anticancer activity, numerous antioxidant, antiparasitic, antihelmintics, antiproliferative, antiHIV, anticonvulsant, anti-inflammatory, antihypertensive, antineoplastic, proton pump inhibitor and antitrichinellosis. Benzimidazoles possess significant biological activities likepotential antitumor agents, smooth muscle cell proliferation inhibitors and in various areas of chemistry.

References

  1. Spasov A.A. and Yozhitsa I.N., Benzimidazole derivatives: spectrum of pharmacological activity and toxicological properties, J. Pharm. Chem., 33, 232-243 (1999)
  2. Mavrova A.T.S., Anichina K.K. and Vuchev D.I., Synthesis and antitrichinellosis activity of some 2-substituted-[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-ones, Bioorg. Med. Chem., 13(9), 5550-5559 (2005)
  3. Goker H., Kus C. and Boykin D.W., Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against Candida species, Bioorg. Med. Chem., 10, 2589-96 (2002)
  4. Goker H., Kus C., Boykin D.W., Synthesis and Potent Antibacterial Activity against MRSA of Some Novel 1,2-Disubstituted-1-Benzimidazole--alkylated-5-carboxamidines, Eur. J. Med. Chem., 40, 1062 (2005)
  5. Andrzejewska M. and Yepez M.L. Synthesis, antiprotozoal and anticancer activity of substituted 2-trifluoromethyl- and 2-pentafluoroethylbenzimidazoles, Eur. J. Med. Chem., 37, 973 (2002)
  6. Ozden S., Atabey D. and Goker H., Synthesis and potent antimicrobial activity of some novel methyl or ethyl 1H-benzimidazole-5-carboxylates derivatives carrying amide or amidine groups, Bioorg. Med. Chem., 13, 1587-97 (2005)
  7. Ramla M.M. and Omar M.A., Discovery and optimization of pyrrolo[1,2-] pyrazinones leads to novel and selective inhibitors of PIM kinases, Bioorg. Med. Chem., 14, 7372 (2006)
  8. Boiani M. and Gonzalez M., Imidazole and benzimidazole derivatives as chemotherapeutic agents, Mini Rev. Med. Chem., 409-424 (2005)
  9. János Béahdy, Recent Developments of Antibiotic Research and Classification of Antibiotics According to Chemical Structure, Advances in Applied Microbiology 18, 309–406(1974)
  10. Devender Pathak, Nadeem Siddiqui, Bhanupriya Bhrigu, Waquar Ahsan, M. Shamsher Alam, Benzimidazoles: A New Profile of Biological Activities, Der Pharmacia Lettre, 2(2), 27-34(2010)
  11. Y. He, B. Wu, J. Yang, D. Robinson, L. Risen, L.B. Ranken, S. Sheng & E. Swayze., Bioorg. Med.Chem. Lett.,13(19), 3253-6 (2003)
  12. Kumar, B. V. S., Vaidya, S. D., Kumar, R.V., Bhirud, S.B., Mane, R.B.. Synthesis and anti-bacterial activity of some novel 2-(6-fluorochroman-2-yl)-1-alkyl/acyl/aroyl-1H-benzimidazoles, Eur. J. Med. Chem.,41, 599604 (2006) DOI PMid:16527375
  13. JT Leonard; L Jeyaseeli; M Kumar; R Sivakumar. Synthesis, anti-inflammatory and antibacterial activities of 4-substituted phenyl benzimidazoles, Asian J. Chem, 18, 1104-1106 (2006)
  14. Deshmukh M.B., Suryavanshi A.W., Deshmukh S.A., Jagtap S.A., Microwave assisted synthesis of 2,3,4-trisubstituted 1,2- dihydropyrimido-[1,2-]benzimidazole, Ind. J. Chem., 86B, 302-305 (2009)
  15. KF Ansari; C Lal. ‘Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents’, Eur. J. Med. Chem., 44, 2294-2299 (2009)
  16. Kazimierczuk Z., Upcroft, J.A., Upcroft, P., Gorska, A., Starosciak, B., Laudy, A., Synthesis, antiprotozoal and antibacterial activity of nitro- and halogeno-substituted benzimidazole derivatives, Acta Biochim. Pol., 49(1), 185-95, (2002)
  17. Ansari K.F. and Lal C., Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents, Eur. J.Med. Chem., 44, 2294-99 (2009)
  18. Ansari K.F. and Lal C., ynthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives, Eur. J. Med. Chem., 44(11), 4028-33 (2009)
  19. Gupta S.P. and Rani S., Synthesis and fungitoxicity of some 5-substituted- 3-polynitrophenyl rhodanines, J. Ind. Chem. Soc., LIV, 478 (1997)
  20. Ghoneim K.M., Essawi M.Y.H., Mohamed M.S., Kamal A.M., Synthesis of 2-[(4-amino or 2,4-diaminophenyl)sulfonyl] derivatives of benzimidazole, benzothiazole and 6-methyluracil as potential antimicrobial agents, Ind. J. Chem., 37B, 904 (1998)
  21. Mane D.V., Shinde D.B., Thore S.N. and Shingare M.S., Synthesis and biological activity of some new 2-alkyl-1-(l-dihydroxypyridyl-methyl)benzimidazoles, Ind. J. Chem., 34B, 917 (1995)
  22. Mavrova A.T., Anichina K.K., Vuchev D.I., Tsenov J.A., Denkova P.S., Magdalena S.K., Micheva M.K., Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives, Eur. J. Med. Chem., 41, 1412-20 (2006)
  23. Yadav S., Kumar P., Clercq E.D., Balzarini J., Pannecouque C., Dewan S.K., Narasimhan B., 4-[1-(Substituted aryl/alkyl carbonyl)-benzoimidazol-2-yl]-benzenesulfonic acids: Synthesis, anti-microbial activity, QSAR studies, and anti-viral evaluation, Eur. J. Med. Chem., 45, 5985-5997 (2010) DOI PMid:20971531
  24. Vitale G., Carta A., Loriga M., Paglietti G., Colla P., Busonera B., Collu D., Loddo R., 2-Arylbenzimidazoles as Anti-viral and Anti-proliferative Agents-Part 1, Med. Chem., 605-615 (2008) DOI PMid:18991746
  25. Budow S., Kozlowska M., Gorska A., Kazimierczuk Z., Eickmeier H., Colla, P.L.,Gosselin, G., Seela, F. Substituted benzimidazoles: anti-viral activity and synthe-sis of nucleosides. ARKIVOC iii: 225- 250(2009)
  26. R. V. Devivar, E. kawashima, Benzimidazole ribonucleosides: design,synthesis, and antiviral activity of certain 2-(alkylthio)-and 2-(benzylthio)-5,6-dichlro-1-(d-ribofuranosyl)benzimidazoles, J. Med. Chem., 37, 2942-2949(1994)
  27. Pandey, V.K., Shukla, A., Synthesis and biological activity of isoquinolinyl benzimidazoles, Ind. J. Chem., 38B, 1381(1999)
  28. Yadav, L. D. S., Pal, D.R., Synthesis and antiviral activity of new 1,3,4-dithi(thiadi)azino(4,5-a) benzimidazole derivatives involving oxidative N-S and N-N bond formations, Ind. J. Chem. 35B, 111(1996)
  29. Kristina S., Marijeta M., Katja E., Ivan S., Magdalena G., Kresimir P., Grace, K. Z., Synthesis, antiviral and antitumor activity of 2-substituted-5-amidino-benzimidazoles, Bioorg. Med. Chem. 15, 4419-4422(2007)
  30. Bishnoi A., Pandey V. K., Saxena R., Synthesis and characterization of benzimida-zolylphenothiazine derivatives and a studyof their antiviral and antifungal activities, Ind. J. Chem.,41B, 1978(1978)
  31. JT Leonard, L Jeyaseeli, M Kumar, R Sivakumar, Synthesis, anti-inflammatory and antibacterial activities of 4-substituted phenyl benzimidazoles, Asian J. Chem., 18, 1104-1106 (2006)
  32. Khan S. A., Nandan S. A., 2-Substituted benzimidazoles as anti-inflammatory and analgesic agents, Indian J. Heterocycl. Chem.,7(1), 55-58 (1997)
  33. Evans D., Hicks T. A., Williamson W. R. N., Meacock S. C. R., Kitchen E. A., Synthesis of a group of 1H–benzimidazoles and their screening for antiinflammatory activity, Eur. J. Med. Chem., 31, 635 (1996)
  34. ZA Alagoz; C Kus T Coban., Synthesis and antioxidant properties of novel benzimidazoles containing substituted indoles, J. Enz. Inhib. Med. Chem., 20(3), 325-331 (2004)
  35. R.A. Michael, K.E.Dennis, A. K. Bhattacharjee., Efficacy of Proton Pump Inhibitor Drugs against Plasmodium falciparum In Vitro and Their Probable Pharmacophores, Antimicrob. Agent Chemother., 46(8), 2627-32 (2002)
  36. G. Sachs, E. Carison & P. Lindberg., Gastric H,K-ATPASE as Therapeutic Target, Annual Review of Pharmacology and Toxicology, 28, 269-284 (1988)
  37. B.Wallmark & O.Lorentzon,J. Gastroenterol,The mechanism of action of omeprazole--a survey of its inhibitory actions in vitro, Scand J Gastroenterol Suppl.20(108), 37-51(1985)
  38. H.Larsson & E. Carlson, Inhibition of gastric acid secretion by omeprazole in the dog and rat, J. Gastroenterol., 85(4), 900-907 (1983)
  39. V. Figala, K. Klemm & B. Kohl., Acid activation of (H+–K+)-ATPase inhibiting 2-(2-pyridylmethyl-sulphinyl)benzimidazoles: isolation and characterization of the thiophilic ‘active principle’ and its reactions, J. Chem. Soc., Chem. Commun., 125-127 (1986)
  40. Lindberg P, Nordberg P, Alminger T, Brändström A, Wallmark B., The mechanism of action of the gastric acid secretion inhibitor omeprazole, 29(80), 13271329 (1986)
  41. JB Bariwal; AK Shah; MK Kathiravan; RS Somani; JR Jagtap; KS Jai ‘Synthesis and antiulcer activity of novel pyrimidylthiomethyl and Pyrimidylsulfinylmethyl benzimidazoles as potential reversible proton pump inhibitors’, Ind. J. Pharm. Ed. Res., 42, 225-231 (2008)
  42. JS Shukla; S Saxena; R Rastogi, Synthesis of some newer, 1-heterocyclic amino/iminomethyl-2-substituted benzimidazoles as a potent CNS, anticonvulsant and monoamine oxidase inhibitory agents, Curr. Sci., 51(17), 820-822 (1982)
  43. Mavrova AT, Anichina KK, Vuchev DI, Issenov JA, Denkova PS, Kondeva MS, Micheva MK ,Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol- 2-ylthioacetylpiperazine derivatives, Eur J Med Chem, 41,1412–1420 (2006)
  44. Lopez-Vallezo F, Medina-Franco JS, Hernandez-Campos A, Rodriguez- Morales S, Yepez L, Cedillo R, Castillo R Molecular modeling of some 1H-benzimidazole derivatives with biological activity against Entamoeba histolytica: a comparative molecular field analysis study, Bioorg Med Chem, 15,1117–1126(2007)
  45. Croft S. L., Yardley V., Chemotherapy of leishmaniasis, Curr. Pharm. Des., 8(4), 319-342 (2002)
  46. R.R. Tidwell, S.K. Jones, N.A. Naiman, L.C. Berger, W.B. Brake, C.C. Dykstra, J.E. Hall, Activity of cationically substituted bis-benzimidazoles against experimental Pneumocystis carinii pneumonia, Antimicrobial Agents and Chemotherapy, 37(8), 1713-1716 (1993)
  47. D. W. Boykin, A. Kumar, J. Spychala, M. Zhou, R. Lombardy, W. D. Wilson, C. C. Dykstra, S. K. Jones, J. E. Hall, R. Tidwell, C. Laughton, C. M. Nunn & S. Neidle, Dicationic diarylfurans as anti-Pneumocystis carinii agents, J. Med. Chem., 38(6), 912-916 (1995)
  48. Cushion M. T.; Walzer P. D.; Ashbaugh A.; Rebholz S.; Brubaker R.; Vanden E. J. J.;Mayence A.; Huang T. L., In vitro selection and in vivo efficacy of piperazine- and alkanediamide-linked bisbenzamidines against Pneumocystis pneumonia in mice, Antimicrob Agents Chemother, 50(7), 2337-43 (2006)
  49. A. Mayence, E.J. Vanden, L. LeCour, L.A. Walker, B.L. Tekwani & T.L. Huang, Piperazine-linked bisbenzamidines: a novel class of antileishmanial agents, Eur. J. Med. Chem., 39(6), 547-553 (2004)
  50. T.G. Hector, E.H. Nunez, I.L. Rivera & J.G Alvarez., Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids, Bioorg. Med. Chem. Lett., 18(110), 3147-51 (2008)
  51. A.T.Mavrova, K. K. Anichina, D. I. Vuchev, J.A. Tsenov, P.S. Denkova, S. Kondeva Magdalena & M.K. Micheva, Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives, Eur. J. Med. Chem., 41(12), 1412-20 (2006)
  52. Kumar D, Jacob MR, Reynolds MB, Kerwin SM Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1, Bioorg Med Chem, 10(12), 3997–4004 (2002)
  53. Vedula MS, Pulipaka AB, Venna C, Chintakunta VC, Jinnapally S, Kattuboina VA, Vallakati RK, Basetti V, Akella V, Rajgopal S, Reka AK, Teepireddy SK, Mamnoor PK, Rajagopalan R, Bulusu G, Khandelwal A, Upreti VV, Mamidi SR New styryl sulfones as anticancer agents, Eur J Med Chem, 38(9), 811–824 (2003)
  54. Ramla MM, Omar MA, Tokuda H, El-Diwani HI Synthesis and inhibitory activity of new benzimidazole derivatives against Burkitt’s lymphoma promotion, Bioorg Med Chem,15(19), 6489–6496 (2007)
  55. Hranjec, M., Starcevic, K., Pavelic, S.K., Lucin, P., Pavelic, K., Zamola, G.K., Synthesis, spectroscopic characterization and antiproliferative evaluation in vitro of novel Schiff bases related to benzimidazoles, Eur. J. Med. Chem., 46(6), 22742-279 (2011)
  56. Gellis A., Kovacic H., Boufatah N., Vanelle P., Synthesis and cytotoxicity evaluation of some benzimidazole-4,7-diones as bioreductive anticancer agents, Eur. J. Med. Chem., 43(9), 1858-1864(2008)
  57. Sondhi SM, Rajavanshi S, Johar M, Bharti N, Azam A, Singh K Anti-inflammatory, analgesic and antiamoebic activity evaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines, Eur J Med Chem., 37(10), 835–843(2002)
  58. Demirayak, S., Mohsen, U.A., Karaburun, A.C. Synthesis and anticancer and anti-HIV testing of some pyrazino[1,2-a]benzimidazole derivatives, Eur. J. Med. Chem., 37(3), 255-260(2002)
  59. Refaat, H.M., Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives, Eur. J. Med. Chem., 45(7), 2949-60 (2010)
  60. BB Kumar, PV Rao, Synthesis and structural studies on transition metal complexes derived from 1-(2-thienyl)-1-ethanole-1-benzimidazole, Asian J. Chem., 18, 3060-3064(2006)