Add time:08/30/2019         Source:sciencedirect.com

Nucleotide heterodimers were synthesized and examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1), including HIV-1 reverse transcriptase (RT) inhibitor-resistant mutants. 3′-Azido-3′-deoxythymidilyl-(5′)-phospho-(5′)-6-[(3′,5′-dimethylphenyl)thio]-5-ethyl-1-[(2-hydroxyethoxy)methyl]uracil (AZT-P-E-HEPU-dM 3′-azido-3′-deoxythymidilyl-(5′)-phospho-(5′)-2′,3′-dideoxyinosine (AZT-P-ddI) proved to be highly potent and selective inhibitors of HIV-1 (IIIB strain) in MT-4 cells. The mechanism of inhibition by these heterodimers may be attributed to their degradation and the formation of each constituent. AZT-P-E-HEPU-dM was also markedly inhibitory to an AZT-resistant mutant (HIV-1-IIIBAZT) and an E-HEPU-dM-resistant mutant (HIV-1-IIIB–R). However, AZT-P-ddI was found to have a less inhibitory effect on HIV-1-IIIBAZT than on HIV-1-IIIB. The heterodimers of (5′,5′) AZT and ribavirin (AZT-P-Ribavirin) and (5′,5′) ddI and ribavirin (ddI-P-Ribavirin) were also synthesized: AZT-P-Ribavirin inhibited HIV-1 replication, but ddI-P-Ribarvirin did not.

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