“A step further in the discovery of phthalein derivatives as Thymidylate Synthase inhibitors”

Phenolphthalein (Pth) was discovered as a low micromolar inhibitor of the enzyme ThymidylateSynthase (TS), an important target for anticancer chemotherapy. In the present work, a newseries of Pth derivatives have been designed and synthesized. All the compounds have beencharacterized through NMR techniques. A set of twelve Pth derivatives has been tested againstthree TS enzymes and their bio-profiles obtained. The bio-profiling studies suggest that theinhibitory potency of the compounds has been improved of about fifty times againstLactobacillus casei TS (LcTS) and five times against humant TS (hTS) with respect to the lead.The most active compound shows an inhibition constant (Ki) of 70 nM against Escherichia coliTS (EcTS).