Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase

SERGIO H. SZAJNMAN; BRUNO N. FALCONE; JUAN B. RODRIGUEZ

EXPERT OPINION ON DRUG DISCOVERY

INFORMA HEALTHCARE

Lugar: London; Año: 2016 vol. 11 p. 307 - 320

1746-0441

Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate to give rise to one molecule of geranyl diphosphate, which on a further reaction with another molecule of isopentenyl diphosphate forms the 15-carbon isoprenoid farnesyl diphosphate. This molecule is the obliged precursor for the biosynthesis of sterols, ubiquinones, dolichols, heme A, and prenylated proteins. The blockade of FPPS prevents the synthesis of farnesyl diphosphate and the downstream essential products. Due to its crucial role in isoprenoid biosynthesis, this enzyme has been winnowed as a molecular target for the treatment of different bone disorders and to control parasitic diseases, particularly, those produced by trypanosomatids and Apicomplexan parasites.