New indazole-indolizine-triazine hybrid molecules with farnesyltransferase inhibitory activity

Abstract

A new series of indazole-indolizine-triazine hybrid molecules was obtained by [3 + 2] cycloaddition reaction between newly synthesized nitrogen ylides with indazole skeleton and previously reported dipolarophile 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine and fully characterized. The biological evaluation of hybrids revealed good antitumor growth inhibitory activity against UO-31 renal cancer cell line for the (1H-indazole-1-yl)(1-(4,6-dimethoxy-1,3,5-triazin-2-yl)-7-methylindolizin-3-yl)methanone derivative 7a. Also, for the same compound, a moderate farnesyltransferase inhibitory activity (IC50 = 52.50 ± 16.07 µM) was observed. However, the best result as farnesyltransferase inhibitor of the series was registered for the 5-bromoindazole substituted analogue 7e (IC50 = 27.08 ± 4.93 µM).

Keywords

• Hybrid molecules
• Indolizine
• S-triazine
• Indazole
• Farnesyltransferase inhibitors
• In vitro anticancer activity