Piperlongumine derived cyclic sulfonamides (sultams): Synthesis and in vitro exploration for therapeutic potential against HeLa cancer cell lines

Abstract

A novel modification of piperlongumine is designed, bearing a cyclic sulphonamide (sultam) and its synthesis is described. For the first time herein we report the synthesis and biological evaluation of the natural product derived cyclic sulfonamides using Grubbs second generation catalyst (Grubbs II) via ring closing metathesis approach. Synthesis of a series of piperlongumine derived sultams is done in a moderate to good yield using Wittig reaction, Ring-Closing Metathesis (RCM) and, amide synthesis by using mixed anhydride, approach. All synthesized compounds were evaluated for anticancer activity and some demonstrated dose dependent reduction in HeLa cell growth. Of these 7, 10 and 14 significantly reduced the cell growth. Consequently their calculated GI₅₀ values were found to be 0.1 or <0.1 μM.

Keywords: Anticancer; GI(50) values; Piperlongumine (PL) derived cyclic sulfonamide (sultams); Ring closing metathesis.