RESUMO
The discovery of azidothymidine's (AZT) activity against human immunodeficiency virus (HIV) provided strong rationale for the design of additional thymidine analogues. One drawback of many nucleoside analogues is the toxicity that often arises due to phosphorylation by cellular kinases. In order to overcome this problem, a number of truncated nucleosides lacking the 4'-hydroxymethyl group have been synthesized. In that regard, the synthesis and preliminary biological results for two truncated carbocyclic thymidine analogues are presented herein.
Assuntos
Antivirais/química , Antivirais/farmacologia , Timidina/análogos & derivados , Timidina/farmacologia , Antivirais/síntese química , Linhagem Celular , Humanos , Timidina/síntese química , Vírus/efeitos dos fármacosRESUMO
The design, synthesis, and unexpected inhibitory activity against S-adenosyl-homocysteine (SAH) hydrolase (SAHase, EC 3.3.1.1) for a series of truncated carbocyclic pyrimidine nucleoside analogues is presented. Of the four nucleosides obtained, 10 was found to be active with a Ki value of 5.0 microM against SAHase.
