Synthesis and anti-breast cancer evaluation of new bakuchiol derivatives

  • Bioorg Med Chem Lett. 2025 Dec 1:128:130361. doi: 10.1016/j.bmcl.2025.130361.
Hong-Mei Li  1 ,  Jing Zhu  2 ,  Ke Zhong  2 ,  Jie Chen  2 ,  Long Zhao  1 ,  Zhen-Hai Zhang  3 ,  Cheng-Zhu Wu  4
Affiliations
  • 1. School of Pharmacy, Bengbu Medical University, 2600 Donghai Road, Bengbu 233030, Anhui, China; Anhui Province Biochemical Pharmaceutical Engineering Technology Research Center, Bengbu 233030, Anhui, China.
  • 2. School of Pharmacy, Bengbu Medical University, 2600 Donghai Road, Bengbu 233030, Anhui, China.
  • 3. Department of Emergency Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, Anhui, China.
  • 4. School of Pharmacy, Bengbu Medical University, 2600 Donghai Road, Bengbu 233030, Anhui, China; Anhui Province Biochemical Pharmaceutical Engineering Technology Research Center, Bengbu 233030, Anhui, China. Electronic address: [email protected].
PMID: 40774392 DOI: 10.1016/j.bmcl.2025.130361
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.

Keywords
Apoptosis; Bakuchiol; Invasion; Migration; Triple-negative breast cancer.
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