[Adducts of 3'-azido-2,3'-dideoxythymidine 5'-phosphate or 5'-phosphonate as inhibitors of cytopathic effect and transformation of cells under the influence of retroviruses in cell culture].
Inhibition of HIV-1- or HIV-2-induced cytopathicity and (Moloney) murine sarcoma virus (MSV)-induced cell transformation by amino acid and amino alcohol adducts of either 3'-azido-2',3'-dideoxythymidine 5'-monophosphate (AZTMP) or 5'-hydrogenphosphonate (AZTHP) were investigated. Both types of nucleotide adducts inhibited replication of HIV-1 and HIV-2 in MT-4 cells at a 1.5- to 3-fold higher EC50 (50% effective concentration) than AZT; and, also, selectivity indexes of these adducts were approximately 1.5 to 3-fold lower than that of AZT. The activity of the AZTMP and AZTHP adducts against MSV-induced transformation of C3H/3T3 cells was equal to or only slightly inferior than that of AZT, but their toxicity was 10-fold lower, so that their selectivity indexes were 2- to 7-fold higher. The nature of the aminoacyl component of the adducts significantly influence the antiretroviral activity of the test compounds.
Fedorov
I I
II
Kraevskiĭ
A A
AA
Bal'zarinin
Zh
Zh
De Klerk
E
E
D016475:3T3 Cells; D000818:Animals; D002472:Cell Transformation, Viral / Q000187:drug effects*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D054306:Dideoxynucleotides; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D013942:Thymine Nucleotides / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; C057287:3'-azido-3'-deoxythymidine 5'phosphate; D015215:Zidovudine
Addukty 5'-fosfata ili 5'-fosfonata 3'-azido-2,3'-didezoksitimidina kak ingibitory tsitopaticheskogo éffekta i transformatsii kletok pod deĭstviem retrovirusov v kletochnykh kul'turakh.