Design, synthesis and biological evaluation of 7–(5–((substituted – amino)-methyl)-thiophen–2–yl)-spiro-[chroman–2,4′–piperidin]–4–one hydrochloride analogues as anticancer agents

Abstract

A series of thirty-one novel 7–(5–((amino)-methyl)-thiophen–2–yl)-spiro-[chroman–2,4′–piperidin]–4–one hydrochloride analogues (Cst 1 – 31) have been designed, synthesized and characterized by 1H NMR, 13C NMR and MS spectral analysis. Here, we evaluated the anticancer potential and biological results of low-molecular-weight bridgehead oxygen and nitrogen-containing spirochromanones on proliferation and apoptosis of the human breast cancer cell line (MCF–7) and Murine melanoma (B16F10). The anticancer activity ranged from 2.9 to 35.0 µM. The most potent compounds Cst-22, Cst-24 and Cst-31 were found to be less toxic against human embryonic kidney (HEK-293) cell lines. Cst-24 and Cst-31 were found to be causing significant cytotoxicity through apoptotic cell death and also G2 phase arrest of cell cycle in B16F10 cells. In-silico ADME prediction stidies of the titled compounds were found within the rules outlined, and these compounds may not face any pharmacokinetic associated issues in the mere future upon developmental stage. These conjugates may serve as a lead for the discovery of potential anticancer drug candidate with better therapeutic profile.