Design, synthesis and biological evaluation of new steroidal β-triazoly enones as potent antiproliferative agents

Abstract

β-Triazoly enones are biologically interesting scaffolds, incorporation of such scaffolds into the steroid nucleus may generate new bioactive steroids and further enrich structural types of steroids. In this work, a series of new steroidal β-triazoly enones were synthesized based on click chemistry and Claisen-Schmidt condensation reaction and further evaluated for their antiproliferative activity against a panel of cancer cells. Most of these compounds showed better potency against PC-3 and MGC-803 cells. Particularly, compound 5a inhibited PC-3 and MGC-803 cells potently with the IC₅₀ values of 1.61 and 1.16 μM, respectively, and was less toxic toward GES-1 with an IC₅₀ value of 20.72 μM. Further mechanistic studies showed that compound 5a inhibited migration and invasion of MGC-803 and PC-3 dose-dependently. Treatment with compound 5a varied mRNA levels and protein expression of EMT markers in both cells. Collectively, the steroidal β-triazoly enones could be potentially utilized to develop new anticancer agents with the ability of inhibiting cell migration and invasion.

Keywords: Antiproliferative activity; Migration and invasion inhibition; Steroids; β-Triazoly enones.