Synthesis and Anti-HIV Activity of [AZT]-[TSAO-T] and [AZT]-[HEPT] Dimers as Potential Multifunctional Inhibitors of HIV-1 Reverse Transcriptase

Publisher Website
Google Scholar
Abstract
In an attempt to combine the HIV-inhibitory capacity of 2',3'-dideoxynucleoside (ddN) analogues\ud and non-nucleoside reverse transcriptase (RT) inhibitors (NNRTI), we have designed, synthesized,\ud and evaluated for their anti-HIV activity several dimers of the general formula [ddNl-\ud (CH2),-[NNRTIl. These dimers combine in their structure a ddN such as AZT and a NNRTI\ud such as TSAO-T and HEPT linked through an appropriate spacer between the N-3 of the\ud thymine base of both compounds. The [TSAO-Tl-(CH2),-[AZTl dimers proved markedly\ud inhibitory to HIV-1. Also, if AZT was replaced by thymidine in the dimer molecules, potent\ud anti-HIV-1 activity was observed. However, although the compounds proved inhibitory to HIV-\ud 1, they were less potent inhibitors than the parent compounds from which they were derived.\ud None of the dimers were endowed with anti-HIV-2 activity. In contrast with the TSAO-T\ud monomers, none of the TSAO-T-containing dimers proved markedly cytotoxic to the cells. There\ud was a clear trend toward decreased antiviral potency with lengthening the methylene spacer\ud in the [TSAO-Tl-(CH2),-[AZTl dimersPeer reviewe

This publication has 0 references indexed in Scilit: