Nucleotide Dimers Suppress HIV Expression In Vitro

Abstract

A series of nucleotide homo- and heterodimers [3''-azido-3''-deoxythymidilyl-(5'',5'')-2'',3''-dideoxy-5'' adenylic acid (AZT-P-ddA), 3''-azido-3''-deoxythymidilyl-(5'',5'')-2'',3''-dideoxy;-5''-adenylic acid, 2-cyanoethyl ester [AZT-P(CyE)-ddA], 3''-azido-3''-deoxythymidilyl-(5'',5'')-2'',3''-dideoxy-5''-inosinic acid (AZT-P-ddI), and 3''-azido-3''deoxythymidilyl-(5'',5'')-3''-azido-3''-deoxy-5''-thymidilic acid (AZT-P-AZT)] were synthesized and compared with respect to their anti-HIV and cytotoxic properties to their component monomers in vitro. MT-2 cells were infected with HIV (TM) followed by the addition of drug. The dimers and their respective monomers inhibited HIV-induced syncytia formation, reverse transcriptase production, and the expression of HIV p24 antigen. However, on an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were observed with the heterodimers when compared with their monomers. Nucleotide dimers, such as AZT-P-ddA, should be actively considered for further evaluation as anti-HIV agents.