Phenothiazine-triazole hybrids with antitumor activity by targeting human farnesyltransferase

New phenothiazine-triazole hybrids 1a-j and 2a-h were synthesized and screened for their potential to inhibit human farnesyltransferase and cancer cell growth in vitro . Four points of chemical modulation were followed and allowed to establish new structure-activity relationships in this series. The most active compound on human farnesyltransferase in the current study 1e was compared with chaetomellic acid A and lonafarnib, known potent farnesyltransferase inhibitors, in blocking the cell cycle of K562 cell line. Compound 1e blocked the cell cycle of K562 cells in G2/M phase in the same way as reference lonafarnib, while chaetomellic acid A was inefficient. The study revealed a new collection of phenothiazine-triazole derivatives targeting human farnesyltransferase with promising potential for further development of compounds for oncology.