Synthesis and biological evaluation of new phenothiazine derivatives bearing a pyrazole unit as protein farnesyltransferase inhibitors

Abstract: A new family of protein farnesyltransferase inhibitors, based on a phenothiazine scaffold, was designed and synthesized. The biological evaluation of these products showed that compounds 28 and 30 were the most active, with protein farnesyltransferase inhibition potencies in the low micromolar range. Compounds were also evaluated for their antiproliferative activity on a NCI-60 cancer cell line panel. Indenopyrazole 30 exhibited the most potent in vitro cytostatic activity inhibiting the growth of HCT-116, LOX IMVI and SK-MEL-5 cell lines. [Copyright &y& Elsevier]