TY - JOUR T1 - Mechanism of antiviral and cytotoxic action of (+/-)-6' beta-fluoroaristeromycin, a potent inhibitor of S-adenosylhomocysteine hydrolase. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 718 LP - 724 VL - 39 IS - 6 AU - M Cools AU - J Balzarini AU - E De Clercq Y1 - 1991/06/01 UR - http://molpharm.aspetjournals.org/content/39/6/718.abstract N2 - (+/-)-6' beta-Fluoroaristeromycin (F-C-Ado) is a potent and competitive inhibitor of purified S-adenosylhomocysteine (AdoHcy) hydrolase isolated from murine L929 cells (Ki = 3.1 nM). It also inhibits vaccinia virus and vesicular stomatitis virus replication in L929 cells, at a 90% inhibitory dose (ID90) of 3.5 and 13 microM, respectively. Considering the close correlation that has been found between Ki and ID90 for other AdoHcy hydrolase inhibitors [Biochem. Pharmacol. 38:1061-1067 (1989)], F-C-Ado is a weaker antiviral agent than expected from its Ki value. Nevertheless, the antiviral action of F-C-Ado appears to be targeted at AdoHcy hydrolase. The fact that F-C-Ado is less antivirally active than expected may be due to its further metabolism to its ATP and GTP derivatives. The cytotoxicity of F-C-Ado may be attributed to both its inhibitory effect on AdoHcy hydrolase and the inhibitory effect of its phosphorylated products on host cell RNA synthesis. ER -