Delineation of the molecular mechanisms of nucleoside recognition by cytidine deaminase through virtual screening.

ABSTRACT: Cytidine deaminase (EC 3.5.4.5, CDA), an enzyme of the pyrimidine salvage pathways, is responsible for the degradation and inactivation of several cytidine-based antitumor drugs such as cytarabine, gemcitabine, decitabine, and azacytidine. Thus, CDA inhibitors are highly sought after as compounds to be co-administered with said drugs to improve their effectiveness. Alternatively, the design of antitumor drugs not susceptible to the action of CDA is also regarded as an attractive solution. Herein we describe a virtual screen for CDA ligands based on chemical similarity and molecular docking. The campaign led to the identification of three novel inhibitors and one novel substrate, with a 19 % hit rate, and allowed a significant extension of the structure-activity relationships, also in light

SUBMITTER: Costanzi S 

PROVIDER: S-EPMC3193038 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature