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.