SYNTHESIS OF ANALOGS OF THE BENZODIAZEPINE RO-5-3335, ANTAGONIST OF TAT HIV-1 - BIOLOGICAL EVALUATION BY LUCIFERASE TRANSACTIVATION AND ANTIVIRAL ASSAY

Ro 5-3335 is a benzodiazepine which is an antagonist of the Tat protei n of HIV-1. A series of Ro 5-3335-derived compounds have been synthesi zed in order to evaluate whether opened analogues of the benzodiazepin e tricyclic structure possess biological activity. The analogues are c onstituted by two aromatic rings variously substituted, linked by an a mino acid. The activity of these compounds has been determined by the quantification of both inhibition of Tat activity using a cell-based t ransfection assay and inhibition of HIV replication in acutely infecte d cells. No analogue provided a notable inhibition of Tat-dependent tr ansactivation or any anti-HIV activity.