Design, synthesis, in vitro potent antiproliferative activity, and kinase inhibitory effects of new triarylpyrazole derivatives possessing different heterocycle terminal moieties

Abstract

A new series of triarylpyrazole derivatives having different heterocycle terminal groups have been designed and synthesised. Compounds 1h–j and 1l exhibited the highest mean percentage inhibition against the 58 cancer cell lines at a concentration of 10 μM, and thus were next examined in 5-dose testing mode to detect their IC50 value. The four compounds showed stronger antiproliferative activities upon comparing their results with sorafenib as a reference compound. Among them, compounds 1j and 1l possessing N-ethylpiperazinyl and N-benzylpiperazinyl terminal moiety through ethylene linker showed the greatest values of mean percentage inhibition (97.72 and 107.18%, respectively) over the 58-cell line panel at 10 μM concentration. The IC50 values of compound 1j over several cancer cell lines were in submicromolar scale (0.26 ∼ 0.38 μM). Moreover, the compounds 1j and 1l showed highly inhibitory activities (99.17 and 97.92%) against V600E-B-RAF kinase.

Keywords

• antiproliferative activity
• morpholine
• substituted piperazine
• triarylpyrazole
• v600e-b-raf