Synthesis of novel benzofuran and related benzimidazole derivatives for evaluation of in vitro anti-HIV-1, anticancer and antimicrobial activities

• Published in: Archives of pharmacal research Vol. 29; no. 10; pp. 826 - 833
• Main Authors: Rida, Samia M, El-Hawash, Soad A M, Fahmy, Hesham T Y, Hazzaa, Aly A, El-Meligy, Mostafa M M
• Format: Journal Article
• Language: English
• Published: Korea (South) 01-10-2006
• Subjects: Benzimidazoles - chemical synthesis; Benzimidazoles - pharmacology; Benzofurans - chemical synthesis; Benzofurans - pharmacology; Candida albicans - drug effects; Candida albicans - growth & development; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - virology; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Drug Design; Drug Screening Assays, Antitumor - methods; Female; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - pharmacology; HIV-1 - drug effects; HIV-1 - growth & development; Humans; Microbial Sensitivity Tests - methods; Molecular Conformation; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development
• DOI: 10.1007/BF02973901
• ISSN: 0253-6269

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 and NSC 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 their in vitro anti-HIV-1, anticancer and antimicrobial activity. Compounds 2, 3a, 3b, and 12b showed weak anti-HIV-1 activity. Compound 6 exhibited mild activity against S. aureus, while compound 15 had mild activity towards S. aureus and C. 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.