Abstract

A series of 6-acetyl-coumarin derivatives (2a-n) were synthesized and evaluated for antiretroviral activity in C8166 T-cell line infected with HxBru-Gluc strain of human immunodeficiency virus-1. Michael Addition followed by re-aromatization and subsequent acid-induced elimination of water leads to the formation of coumarin intermediate, which undergoes Claisen-Schmidt condensation with substituted bezaldehydes using silica sulphuric acid as a catalyst to form 6-acetyl-coumarin derivatives, 2a-n. In silico absorption, distribution, metabolism, excretion and toxicity parameters of compounds 2a-n were found within their reference limits. All synthesized compounds were devoid of cytotoxicity as they have shown cell viability count more than 80 % in cytotoxicity assay. Compounds 2a, 2g and 2h showed potent inhibitory activity against human immunodeficiency virus infection with IC₅₀ value of 4.7, 4.5 and 0.35 μM, respectively. It was found that electron-withdrawing group at phenyl ring, attached to the coumarin nucleus was crucial for activity against human immunodeficiency virus. The present study may be helpful in the development of some potent antiretroviral agents.