title: Antiviral activities of nucleotide heterodimers against human immunodeficiency virus type 1 in vitro.
abstract: 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) and 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-IIIB/AZT) 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-IIIB/AZT 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.
authors.affiliation: Rational Drug Design Laboratories, Fukushima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ijichi
authors.forename: M
authors.initials: M
authors.lastname: Fujiwara
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Morozumi
authors.forename: H
authors.initials: H
authors.lastname: Machida
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
authors.forename: K
authors.initials: K
authors.lastname: Konno
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Baba
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D003588:Cytopathogenic Effect, Viral; D016049:Didanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000737:chemistry; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D012254:Ribavirin; D015215:Zidovudine; D014498:Uracil; D016049:Didanosine