3-Phenylcoumarins as Inhibitors of HIV-1 Replication

Molecules

Dionisio Olmedo³  Rocío Sancho¹  Luis M. Bedoya²  José L. López-Pérez³  Esther del Olmo³  Eduardo Muñoz¹  José Alcamí²  Mahabir P. Gupta⁴ 

[1] Department of Cellular Biology, Physiology and Immunology, University of Córdoba, Institute Maimonides for Biomedical Research (IMIBIC). Avda de Menendez Pidal s/n, 14004 Córdoba, Spain;National Microbiology Centre Institute Carlos III, Crt. Majadahonda a Pozuelo, 28220 Majadahonda, Madrid, Spain;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Salamanca, CIETUS-IBSAL, 37007 Salamanca, Spain;CIFLORPAN, Center for Pharmacognostic Research on Panamanian Flora, College of Pharmacy, University of Panama, Box 0824-00172, Panama, Republic of Panama;

关键词: 3-phenylcoumarins;    AIDS;    Tat protein;    NF-κB inhibition;    anti-HIV activity;   

DOI  :  10.3390/molecules17089245

来源: mdpi

【 摘 要 】

We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC₅₀ values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.