Is it still worth renewing nucleoside anticancer drugs nowadays?

Abstract

Nucleoside has situated the convergence point in the discovery of novel drugs for decades, and a large number of nucleoside derivatives have been constructed for screening novel pharmacological properties at various experimental platforms. Notably, nearly 20 nucleosides are approved to be used in the clinic treatment of various cancers. Nevertheless, the blossom of synthetic nucleoside analogs in comparison with the scarcity of nucleoside anticancer drugs leads to a question: Is it still worth insisting on the screening of novel anticancer drugs from nucleoside derivatives? Hence, this review attempts to emphasize the importance of nucleoside analogs in the discovery of novel anticancer drugs. Firstly, we introduce the metabolic procedures of nucleoside anticancer drug (such as 5-fluorouracil) and summarize the designing of novel nucleoside anticancer candidates based on clinically used nucleoside anticancer drugs (such as gemcitabine). Furthermore, we collect anticancer properties of some recently synthesized nucleoside analogs, aiming at emphasizing the availability of nucleoside analogs in the discovery of anticancer drugs. Finally, a variety of synthetic strategies including the linkage of sugar moiety with nucleobase scaffold, modifications on the sugar moiety, and variations on the nucleobase structure are collected to exhibit the abundant protocols in the achievement of nucleoside analogs. Taken the above discussions collectively, nucleoside still advantages for the finding of novel anticancer drugs because of the clearly metabolic procedures, successfully clinic applications, and abundantly synthetic routines.