Motivation: Although natural products represent a reservoir of molecular diversity, the process of isolating and identifying active compounds is a bottleneck in drug discovery programs. The rapid isolation and identification of the bioactive component(s) of natural product mixtures during the bioassay-guided fractionation have become crucial factors in the competition with chemical compound libraries and combinatorial synthetic efforts. In this respect, the use of spectral databases in identification processes is indispensable.

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.