Benzylidene-isophorone hybrids with strong anticancer activity

Abstract

Isophorone is a cyclic ketone that has gained significant attention in the field of organic chemistry due to its versatile reactivity and structural attributes. Derivatives of isophorone offer a broad spectrum of applications ranging from pharmaceuticals to polymer chemistry. With the aim of developing novel hybrid structures based on benzylidene by combining with isophorone scaffold, we report 3 derivatives of the benzylidene-isophorone hybrids and its potent anticancer activity. In order to optimize the anticancer activity of hybrids di-substitution of -Cl group in C₂ and C₆ position of phenyl ring (compound1), -OCH₃ group in C₂ and C₅ position of phenyl ring (compound2), and -OCH₃ group in C₂ and C₃ position of phenyl ring (compound3) of benzylidene (PhCH=) moiety were made. The structure of Compounds1,2 and 3 were elucidated using spectral and XRD methods. Compounds1,2 and 3 exhibit space group P c a 21, P-1, and P 1 21/n 1 respectively. Compounds1,2 and 3 were tested for the potent anticancer activity on MDA MB-231 cell line. All the three compounds exhibit good anticancer activity on the breast cancer cells. The parent hybrid with ortho, ortho directing -Cl (1) exhibits strong antiproliferation effect (IC₅₀ = 0.028 µM) on MDA-MB 231 cell line. However, hybrid structures with ortho, meta directing -OCH₃ (2) group showed moderate effect (IC₅₀ = 0.061 µM) and hybrid with ortho, meta directing -OCH₃ (3) substitution showed the least potent anticancer activity (IC₅₀ = 0.074 µM). The benzylidene-isophorone hybrids exhibit anticancer effects in the following order: 1 > 2 > 3.

Keywords: Anticancer; Benzylidene; Benzylidene-isophorone hybrids; Isophorone; MDA_MB 231 cell line.