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.
ASJC Scopus subject areas
- Infectious Diseases