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Anti-HIV and anti-HBV activity and resistance profile of 2',3'-dideoxy-3'-thiacytidine (3TC) and its arylphosphoramidate derivative CF 1109.

Abstract：

:A novel membrane-soluble prodrug of the 5'-monophosphate derivative of 3TC containing a phenyl group and the methyl ester of L-alanine linked to the phosphorus through a phosphoramidate bond with the primary amino moiety (designated Cf 1109) was prepared. The 3TC prodrug proved less potent an inhibitor of HIV-1 and HIV-2 replication in CEM cell cultures than 3TC, but lost only 20-fold antiviral potency in 2'-deoxycytidine kinase-deficient CEM/dCK- cells compared with a more than 2,000-fold decrease of activity of 3TC. In contrast, 3TC and Cf 1109 proved equally highly effective in inhibiting HBV release in supernatants of HBV-transfected Hep G2 2.2.15 cell cultures (50% effective concentration approximately 0.02 microM). Both compounds easily selected for highly resistant HIV-1 strains at a comparable speed of breakthrough. The mutant viruses contained an 184-Ile and/or 184-Val amino acid change in their reverse transcriptase. Our data are suggestive for a relatively poor delivery of 3TC-MP in the intact CEM cells but a remarkably high delivery of 3TC and/or 3TC-MP in the intact Hep G2 2.2.15 cells.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Balzarini J,Wedgwood O,Kruining J,Pelemans H,Heijtink R,De Clercq E,McGuigan C

doi

10.1006/bbrc.1996.1181

subject

Has Abstract

pub_date

1996-08-14 00:00:00

pages

363-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006291X9691181X

journal_volume

225

pub_type

杂志文章

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