Fluorination of Naturally Occurring N6-Benzyladenosine Remarkably Increased Its Antiviral Activity and Selectivity
作者： Vladimir Oslovsky , Mikhail Drenichev , Liang Sun , Nikolay Kurochkin , Vladislav Kunetsky
DOI: 10.3390/MOLECULES22071219
关键词: Selectivity 、 Toxicity 、 Stereochemistry 、 Potency 、 Enterovirus 71 、 Cytotoxicity 、 High cell 、 Human enterovirus 、 Cytopathic effect 、 Chemistry
摘要: Recently, we demonstrated that the natural cytokinin nucleosides N6-isopentenyladenosine (iPR) and N6-benzyladenosine (BAPR) exert a potent selective antiviral effect on replication of human enterovirus 71. In order to further characterize profile this class compounds, generated series fluorinated derivatives BAPR evaluated their activity 71 in cytopathic (CPE) reduction assay. The monofluorination BAPR-phenyl group changed selectivity index (SI) slightly because concomitant high cell toxicity. Interestingly, incorporation second fluorine atom resulted dramatic improvement selectivity. Moreover, N6-trifluoromethylbenzyladenosine (9–11) exhibited also very interesting profile, with low cytotoxicity observed. particular, analogue N6-(3-trifluoromethylbenzyl)-adenosine (10) four-fold gain potency as compared best SI represents promising candidate for development.
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