Abstract
Previously, we synthesized and evaluated several benzofuran derivatives containing heterocyclic ring substituents linked to the benzofuran nucleus at C-2 by a two- to four-atom spacer as potential anti-HIV-1, anticancer and antimicrobial agents. Among these derivatives,NSC 725612 andNSC 725716 exhibited interesting anti-HIV-1 activity. To further investigate the structure-activity relationship, we synthesized several new benzofuran derivatives derived from 2-acetylbenzofuran (2, 3a-c) and 2-bromoacetylbenzofuran (6; 7a,b; 8a,b). The compounds were designed to comprise the heterocyclic substituents directly linked to the benzofuran nucleus at C-2. Moreover, various related benzimidazoles derived from 2-acetylbenzimidazole and from 2-cyanomethylbenzimidazole (12a,b; 13a,b; 15; 16a,b) were also prepared as isosteres. The synthesized compounds were preliminarily evaluated for theirin vitro anti-HIV-1, anticancer and antimicrobial activity. Compounds2, 3a, 3b, and12b showed weak anti-HIV-1 activity. Compound6 exhibited mild activity againstS. aureus, while compound15 had mild activity towardsS. aureus andC. albicans. However, no significant anticancer activity was observed with any of the tested compounds. From these results, we conclude that the presence of the spacer between the heterocyclic substituent and the benzofuran nucleus may be essential for the biological activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Badawey, E.A. and Kappe, T., Benzimidazole condensed ring systems. XI. Synthesis of some substituted cycloalkyl pyrido[1,2-a]benzimidazoles with anticipated antineoplastic activity.Eur. J. Med. Chem., 34, 663–667 (1999).
Buckheit, R. W. Jr, Hollingshead, M. G., Germany-Decker, J., White, E. L., McMahon, J. B., Allen, L. B., Ross, L. J., Decker, W. D., Westbrook, L., and Shannon, W. M., Thiazolobenzimidazole: Biological and biochemical anti-retroviral activity of a new non-nucleoside reverse transcriptase inhibitor.Antiviral Res., 21, 247–265 (1993).
Conte, J. E. and Barriere, S. L.,Manual of Antibiotics and Infectious Diseases, 1st Ed. Lea and Febiger, U.S.A., 135 (1988).
Copeland, R. A. and Day, A. R., The preparation and reactions of 2-benzimidazolylecarboxylic acid and 2-benzimidazolacetic acid.J. Am. Chem. Soc., 65, 1072–1075 (1943).
Demirayak, S., Abu Mohsen, U., and Cagri Karaburun, A., Synthesis and anticancer and anti-HIV testing of some pyrazino[1,2-a]benzimidazole derivatives.Eur. J. Med. Chem., 37, 255–260 (2002).
El-Hawash, S. A., Badawey, E. A., and Kappe, T., Benzimidazole condensed ring system. XII. Synthesis and anticancer evaluation of certain pyrido[1,2-a]benzimidazole derivatives.Pharmazie, 54, 341–346 (1999).
Elliott, E. D., The preparation and properties of 2-vinylbenzofuran,J. Am. Chem. Soc., 73, 754 (1951).
Ghabrial, S. S., Zaki, M. Y., and Eldin, S. M., Hydrazidoylhalides in heterocyclic synthesis of several new pyrazole[5,1-c]-1,2,4-triazine, pyramidine and thiazole derivatives,Egypt J. Pharm. Sci., 37(1–6) 329–339 (1996).
Grever, M., Schepartz, S., and Chabner, B.,The National Cancer Institute Cancer Drug Discovery and Development Program Semin.Oncol., 19, 622–638 (1992).
Hao, D., Rizzo, J. D., Stringer, S., Moore, R. V., Marty, J., Dexter, D. L., Mangold, G. L., Camden, J. B., Von Hoff, D. D., and Weitman, S. D., Preclinical antitumor activity and pharmacokinetics of methyl-2-benzimidazolecarbamate (FB642).Invest. New Drugs, 20, 261–270 (2002).
Hutchinson, S., Luetjens, H., and Scammells, P., A new synthesis of the benzofuran adenosine antagonist XH-14,Bloorg. Med. Chem. Lett. 7, 3081–3084 (1997).
Kempter, G., Sarodnick, G., Schaefer, H. and Fiebig, H. J., Spindler, Heterocycles from 2-bromoacetyl heterocycles.J. Z. Chem., 8(9) 339–340 (1968), ThroughC. A., 70, 11630b (1969).
Kovalenko, S. N., Vasil’ev, M. V., Sorokina, I. V., ChernyKh, V. P., Turov, A. V., and Rundnev, S. A., Recyclization of 2-imino-2H-1-benzopyrans using nucleophilic reagents3. Reactions of 2-iminocoumarin-3-carboxamides with o-phenylenediamines and o-amino(thio)phenols,Chem. Heterocycl. Comp., 34, 1412–1415 (1999), ThroughC. A., 131, 257452p (1999).
Ozegowski, W. and Krebs, D., Amino acid antagonists IV. Attempted synthesis of [1-methyl-5-bis(b-chloroethyl)amino-benzimidazol-2-yl]acetic acid,J. Prakt. Chem., 29(1–2), 18–25, ThroughC. A., 63, 8341g (1965).
Pieters, L, Van Dyck, S, Gao, M, Bai, R, Hamel, E., and Vlietinck A., Lemi inverted question markere G Synthesis and biological evaluation of dihydrobenzofuran lignans and related compounds as potential antitumor agents that inhibit tubulin polymerization.J. Med. Chem., 42, 5475–5481 (1999).
Pinney, K., Pettit, G., Mocharla, V., Del, P., Majia, M., and Shirali, A., Benzo[b]thiophen derivatives, useful as antimitotic agents which inhibit tubulin polymerization and as antitumor agents, US Appl., 813, 018, 6 Mar. (1997) 85 pp (Eng.),C. A., 129, 245037c (1998).
Reynold, J. E. F.,Martindale The Extra Pharmacopeia, 30thed., Royal Pharmaceutical Society of Great Britain, Pharmaceutical Press, London (a) P 46, 54–55 (b) P 319, (c) P 544 (1993).
Rida, S. M., El-Hawash, S. A., Fahmy, H. T., Hazza, A. A., El-and Meligy, M. M., Synthesis and in vitro Evaluation of some Novel Benzofuran Derivatives as Potential Anti-HIV-1, Anticancer and Antimicrobial Agents.Arch. Pharm. Res., 29, 16–25 (2006).
Scott, A. C., Laboratory Control of Antimicrobial Therapy. In: Colle, J. G., Duguid, J. P., Fraser, A. G., Marmion, B. P., Mackie and MacCartney Practical Medical Microbiology, Churchill Livingstone, 13th edition, 2, 161–181 (1989).
Weislow, O. W., Kiser, R., Fine, D., Bader, J., Shoemaker, R. H., Boyd, M. R., New soluble-formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDS-antiviral activity.J. Natl. Cancer Inst., 81, 577–586 (1989).
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was presented in part at the Second International Conference of Pharmaceutical and Drug Industries Division Poster P. 162, 7–9 March 2005.
Rights and permissions
About this article
Cite this article
Rida, S.M., El-Hawash, S.A.M., Fahmy, H.T.Y. et al. Synthesis of novel benzofuran and related benzimidazole derivatives for evaluation ofin vitro anti-HIV-1, anticancer and antimicrobial activities. Arch Pharm Res 29, 826–833 (2006). https://doi.org/10.1007/BF02973901
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02973901