Synthesis and antiviral activity of some new S-adenosyl-L-homocysteine derivatives.
A series of new S-adenosyl-L-homocysteine (AdoHcy) analogues with modifications to amino acid and nucleoside moieties was prepared via condensation of appropriate nucleoside precursors and suitably protected L-homocystine derivatives. The AdoHcy derivatives as well as the nucleoside precursors were evaluated for their antiviral activity. Some of the compounds, in particular S-tubercidinyl-L-homocysteine propyl ester (36), N-(trifluoroacetyl)-S-tubercidinyl-L-homocysteine isopropyl ester (27), S-3'-deoxytubercidinyl-L-homocysteine (58), N-(trifluoracetyl)-S-tubercidinyl-L-homocysteine propyl ester (26), and N-(methoxyacetyl)-S-tubercidinyl-L-homocysteine ethyl ester (31) showed potent and selective activity against HSV, VV, and VSV. It is likely that they exert their antiviral effect via selective inhibition of the methyltransferases which are required for the maturation of viral mRNAs.
Balzarini
J
J
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, U.K.
De Clercq
E
E
Serafinowski
P
P
Dorland
E
E
Harrap
K R
KR
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D011817:Rabbits; D012435:S-Adenosylhomocysteine / Q000031:analogs & derivatives*; D018139:Simplexvirus / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000998:Antiviral Agents; D012435:S-Adenosylhomocysteine; D008780:Methyltransferases