Synthesis and biological activity study of tanshinone I-pyridinium salt derivatives.

ABSTRACT: Natural product tanshinone I exhibits weak potency and poor drug-like properties, which have restricted its clinical development as an anticancer agent. Herein, twenty novel tanshinone I-pyridinium salt derivatives and a pyridinium salt precursor were designed and synthesized, and their antitumor activities were evaluated. Among these tanshinone I-pyridinium salts, compound a4, bearing a 4-bromobenzoylmethyl substituent at the N-1 position of the pyridine ring, showed the most potent cytotoxicity against breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and prostate cancer (22RV1) cell lines, with IC₅₀ values of 1.40-1.63 μM. Preliminary mechanistic studies suggest that a4 targets PI3Kα with the IC₅₀ of 9.24 ± 0.20 μM and exerts effective inhibition of the

SUBMITTER: Zhao H 

PROVIDER: S-EPMC12332164 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature