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.