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A. N. Korovina, M. V. Yasco, A. V. Ivanov, A. L. Khandazhinskaya, E. V. Karamov, G. V. Kornilayeva, M. K. Kukhanova
New HSV and HIV replication inhibitors on the base of
phosphonate nucleoside analogs
Abstract
Two types of nucleoside analogs were synthesized: acyclic Z-
and E-isomers of 9-[3-(phosphonomethoxy)prop-1-en-1-yl]adenine and
carbocyclic isosteric analog of guanosine monophosphate. Acyclic (Z)-
and (E)- isomers suppressed HSV and HIV replication and were not toxic
for eukaryotic cells. The activity of (Z)- isomer against both viruses
was higher than that of (E)- isomer. Diphosphates of these compounds
demonstrated high substrate activity towards the recombinant HSV DNA polymerase
and HIV reverse transcriptase. The diphosphatephosphonate of the carbocyclic
guanosine analog didn’t display notable substrate activity towards HSV DNA
polymerase but acted as a substrate of HIV RT.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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