Abstract
One-pot synthesis of new biologically active 4-(1H-benzimidazol-2-yl)benzene-l,3-diols has been developed. The compounds were prepared by the reaction of aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s with benzene-l,2-diamines. Their structures were identified using elemental, IR, 1H-NMR, and mass spectra analyses. The developed method offers short reaction times, relatively large-scale synthesis, easy and quick isolation of the products, and good yields. The cytotoxicity in vitro against the 4 human cancer cell lines: SW707 (rectal), HCV29T (bladder), A549 (lung), and T47D (breast) was determined. The antiproliferative properties of some compounds studies were stronger than those of cisplatin, which was used as a comparator drug.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bahrami, K., Khodaei, M. M., and Nejati, A., Synthesis of 1,2-disubstituted benzimidazoles, 2-substituted benzimidazoles and 2-substituted benzothiazoles in SDS micelles. Green Chem., 12, 1237–1241 (2010).
Bhattacharya, S., Chaudhuri, P., Jain, A. K., and Paul, A., Symmetrical bisbenzimidazoles with benzenediyl spacer: the role of the shape of the ligand on the stabilization and structural alterations in telomeric G-quadruplex DNA and telomerase inhibition. Bioconjug. Chem., 21, 1148–1159] (2010).
Biron, K. K., Antiviral drugs for cytomegalovirus diseases. Antiviral. Res., 71, 154–163 (2006).
Brain, C. T. and Brunton, S. A., An intramolecular palladiumcatalysed aryl amination reaction to produce benzimidazoles. Tetrahedron Lett., 43, 1893–1895 (2002).
Brough, P. A., Barril, X., Beswick, M., Dymock, B. W., Drysdale, M. J., Wright, L., Grant, K., Massey, A., Surgenor, A., and Workman, P., 3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone. Bioorg. Med. Chem. Lett., 15, 5197–5201 (2005).
Bruno, R. D., Gover, T. D., Burger, A. M., Brodie, A. M., and Njar, V. C., 17α-Hydroxylase/17,20 lyase inhibitor VN/cancer cells via induction of the endoplasmic reticulum stress response. Mol. Cancer Ther., 7, 2828–2836 (2008).
Gellis, A., Kovacic, H., Boufatah, N., and Vanelle, P., Synthesis and cytotoxicity evaluation of some benzimidazole-4,7-diones as bioreductive anticancer agents. Eur. J. Med. Chem., 43, 1858–1864 (2008).
Kazimierczuk, Z. and Shugar, D., Preparation and properties of the 5,6-dinitro and 4,6(5,7)-dinitro derivatives of benzimidazole and their 1-β-D-ribofuranosides. Nucleosides Nucleotides, 8, 1379–1385 (1989).
Kraut, E. H., Fleming, T., Segal, M., Neidhart, J. A., Behrens, B. C., and MacDonald, J., Phase II study of pibenzimol in pancreatic cancer. A southwest oncology group study. Invest. New Drugs, 9, 95–96 (1991).
Kreusch, A., Han, S., Brinker, A., Zhou, V., Choi, H. S., He, Y., Lesley, S. A., Caldwell, J., and Gu, X. J., Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles. Bioorg. Med. Chem. Lett., 15, 1475–1478 (2005).
Lahue, B. R., Ma, Y., Shipps, G. W., Jr., Seghezzi, W., and Herbst, R., Substituted benzimidazoles: a novel chemotype for small molecule hKSP inhibitors. Bioorg. Med. Chem. Lett., 19, 3405–3409 (2009).
Matysiak, J., Synthesis, antiproliferative and antifungal activities of some 2-(2,4-dihydroxyphenyl)-4H-3,1-benzothiazines. Bioorg. Med. Chem., 14, 2613–2619 (2006).
Matysiak, J. and Niewiadomy, A., Application of sulfinyl bis (2,4-dihydroxythiobenzoyl) in the synthesis of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Synth. Commun., 36, 1621–1630 (2006).
Matysiak, J. and Opolski, A., Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Bioorg. Med. Chem., 14, 4483–4489 (2006).
Peng, G., Ma, L., Liu, B., Cai, J.-B., and Deng, H., Syntheses, structures and photoluminescence of Ln(III)-Cu(I) coordination polymers based on benzimidazole-5-carboxylate and oxalate ligands. Inorg. Chem. Commun., 13, 599–602 (2010).
Penning, T. D., Zhu, G. D., Gandhi, V. B., Gong, J., Liu, X., Shi, Y., Klinghofer, V., Johnson, E. F., Donawho, C. K., Frost, D. J., Bontcheva-Diaz, V., Bouska, J. J., Osterling, D. J., Olson, A. M., Marsh, K. C., Luo, Y., and Giranda, V. L., Discovery of the poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J. Med. Chem., 52, 514–523 (2009).
Penning, T. D., Zhu, G. D., Gong, J., Thomas, S., Gandhi, V. B., Liu, X., Shi, Y., Klinghofer, V., Johnson, E. F., Park, C. H., Fry, E. H., Donawho, C. K., Frost, D. J., Buchanan, F. G., Bukofzer, G. T., Rodriguez, L. E., Bontcheva-Diaz, V., Bouska, J. J., Osterling, D. J., Olson, A. M., Marsh, K. C., Luo, Y., and Giranda, V. L., Optimization of phenylsubstituted benzimidazole carboxamide poly(ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)pheny)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious inhibitor. J. Med. Chem., 53, 3142–3153 (2010).
Perry, R. J. and Wilson, B. D., A novel palladium-catalyzed synthesis of 2-arylbenzimidazoles. J. Org. Chem., 58, 7016–7021 (1993).
Pescovitz, M. D., Maribavir: a new oral anti-cytomegalovirus drug. Future Virol., 3, 435–443 (2008).
Ranganatha, S. R., Kavitha, C. V., Vinaya, K., Prasanna, D. S., Chandrappa, S., Raghavan, S. C., and Rangappa, K. S., Synthesis and cytotoxic evaluation of novel 2-(4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-ylthio)-1H-benzo[d] imidazole derivatives. Arch. Pharm. Res., 32, 1335–1343 (2009).
Refaat, H. M., Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur. J. Med. Chem., 45, 2949–2956 (2010).
Singh, S., Ojha, H., Tiwari, A. K., Kumar, N., Singh, B., and Mishra, A. K., Design, synthesis, and in vitro antiproliferative activity of benzimidazole analogues for radiopharmaceutical efficacy. Cancer Biother. Radiopharm., 25, 245–250 (2010).
Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 82, 1107–1112 (1990).
Tavman, A. and Birteksoz, A. S., Spectral characterization and antimicrobial activity of 4-(5-H/Me/Cl/NO2-1H-benzimidazol-2-yl)-benzene-1,3-diols and some metal complexes. Rev. Inorg. Chem., 29, 255–272 (2009).
Thomas, H. D., Calabrese, C. R., Batey, M. A., Canan, S., Hostomsky, Z., Kyle, S., Maegley, K. A., Newell, D. R., Skalitzky, D., Wang, L. Z., Webber, S. E., and Curtin, N. J., Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol. Cancer Ther., 6, 945–956 (2007).
Tong, Y., Bouska, J. J., Ellis, P. A., Johnson, E. F., Leverson, J., Liu, X., Marcotte, P. A., Olson, A. M., Osterling, D. J., Przytulinska, M., Rodriguez, L. E., Shi, Y., Soni, N., Stavropoulos, J., Thomas, S., Donawho, C. K., Frost, D. J., Luo, Y., Giranda, V. L., and Penning, T. D., Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents. J. Med. Chem., 52, 6803–6813 (2009).
Vitale, G., Carta, A., Loriga, M., Paglietti, G., La Colla, P., Busonera, B., Collu, D., and Loddo, R., 2-Arylbenzimidazoles as antiviral and antiproliferative agents. Part 1. Med. Chem., 4, 605–615 (2008).
Vitale, G., Corona, P., Loriga, M., Carta, A., Paglietti, G., La Colla, P., Busonera, B., Marongiu, E., Collu, D., and Loddo, R., 2-Arylbenzimidazoles as antiviral and antiproliferative agents. Part 2. Med. Chem., 5, 507–516 (2009).
White, A. W., Almassy, R., Calvert, A. H., Curtin, N. J., Griffin, R. J., Hostomsky, Z., Maegley, K., Newell, D. R., Srinivasan, S., and Golding, B. T., Resistance-modifying agents. 9. Synthesis and biological properties of benzimi dazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase. J. Med. Chem., 43, 4084–4097 (2000).
Won, M. S., Im, N., Park, S., Boovanahalli, S. K., Jin, Y., Jin, X., Chung, K. S., Kang, M., Lee, K., Park, S. K., Kim, H. M., Kwon, B. M., Lee, J. J., and Lee, K., A novel benzimidazole analogue inhibits the hypoxia-inducible factor (HIF)-1 pathway. Biochem. Biophys. Res. Commun., 385, 16–21 (2009).
Yang, D., Fokas, D., Li, J., Yu, L., and Baldino, C. M., A versatile method for the synthesis of benzimidazoles from o-nitroanilines and aldehydes in one step via a reductive cyclization. Synthesis, 47–56 (2005).
Zhang, D., Wang, Z., Xu, W., Sun, F., Tang, L., and Wang, J., Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles. Eur. J. Med. Chem., 44, 2202–2210 (2009).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Karpińka, M.M., Matysiak, J. & Niewiadomy, A. Synthesis of novel 4-(1H-benzimidazol-2-yl)benzene-1,3-diols and their cytotoxic activity against human cancer cell lines. Arch. Pharm. Res. 34, 1639–1647 (2011). https://doi.org/10.1007/s12272-011-1008-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-011-1008-0