title: [Synthesis and evaluation of novel nucleic acid derivatives as bioactive substances].
abstract: This review describes the synthesis and evaluation of novel nucleic acid derivatives performed by our research group to date. We developed a new method for the synthesis of 2-alkoxyadenosine analogs via nonaqueous diazotization-dediazoniation reactions. By applying these reactions, we effectively synthesized four types of carbocyclic oxetanocin analogs (2-alkoxy-C.OXT-A). The angiogenic activities of these compounds were evaluated using human umbilical vein endothelial cells. This resulted in increased activities of the analogs, especially of 2-methoxy-C.OXT-A and 2-isopropoxy-C.OXT-A, at a concentration of 100 μM; they showed angiogenic potency similar to or greater than that of vascular endothelial growth factor. We also synthesized and evaluated a novel series of uracil derivatives carrying a 3,5-dimethylbenzyl group at the N(3)-position and acting as non-nucleoside HIV-1 reverse transcriptase inhibitors. Some of these compounds showed good-to-moderate inhibitory activity, with EC₅₀ values in the submicromolar range. Among them, the analog 6-amino-1-(4-picolyl)-uracil showed significant HIV-1 reverse transcriptase inhibition, with an EC₅₀ value of 0.03 μM and a high selectivity index of 2863.
authors.affiliation: Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Sakakibara
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D009696:Nucleic Acids / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D009696:Nucleic Acids; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase