Synthesis and anti-breast cancer evaluation of new bakuchiol derivatives.

Abstract

In this study, we semi-synthesized nineteen new derivatives of bakuchiol and evaluated their anti-breast cancer properties. Among them, compound 19 stood out as the most effective demonstrating significant cytotoxic activity against MDA-MB-231 cells, with IC₅₀ values of 4.13 μM. Notably, the cytotoxicity of compound 19 towards normal mouse hepatocytes (Aml-12) cells was considerably lower, with IC₅₀ values of 31.60 μM. Our findings indicated that compound 19 triggered apoptosis in MDA-MB-231 cells by increasing the levels of Bax and Cyt C, reducing Bcl-2, and initiating caspase-3 cleavage. It also suppressed the invasion and migration of MDA-MB-231 cells by down-regulating MMP-2 and MMP-9 expression and up-regulating E-cadherin protein levels. We further demonstrated that compound 19 significantly suppressed tumor growth in nude mice xenografted with MDA-MB-231 cells.