Inhibition of CTP synthase from Escherichia coli by xanthines and uric acids

CTP synthase (CTPS) catalyzes the conversion of UTP to CTP and is a recognized target for the development of anticancer, antiviral, and antiprotozoal agents. Xanthine and related compounds inhibit CTPS activity (IC50 = 0.16–0.58 mM). The presence of an 8-oxo function (i.e., uric acids) enhances inhibition (IC50 = 0.060–0.121 mM). An intact purine ring with anionic character favors inhibition. In general, methylation of the purine does not significantly affect inhibition.

Xanthines, uric acids, and their methylated derivatives inhibit CTP synthase-catalyzed CTP formation from UTP (IC50 = 0.060–0.58 mM).Figure optionsDownload as PowerPoint slide