All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

Abstract

Synthesis and Antiretroviral Activity of 6-Acetyl-coumarin Derivatives against HIV-1 Infection

Author(s): V. K. Srivastav, M. Tiwari*, X. Zhang and X-J. Yao
Department of Pharmacy, Laboratory of Medicinal and Pharmaceutical Chemistry, Shri G. S. Institute of Technology and Science, 23 Park Road, Indore-452 003, India, Department of Medical Microbiology, Laboratory of Molecular Human Retrovirology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0W3, Canada

Correspondence Address:
Department of Pharmacy, Laboratory of Medicinal and Pharmaceutical Chemistry, Shri G. S. Institute of Technology and Science, 23 Park Road, Indore-452 003, India, E-mail: [email protected]


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.

Full-Text | PDF