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Synthesis and biological evaluation of geldanamycin-ferulic acid conjugate as a potent Hsp90 inhibitor.

ABSTRACT: A novel geldanamycin-ferulic acid conjugate LZY228 was prepared and evaluated for anti-proliferation activity on human cancer cell line MDA-MB-231. Compound LZY228 exhibited potent cytotoxicity with IC₅₀ value of 0.27 μM, which was more potent than 17-AAG. Hepatotoxicity test in mice demonstrated that the levels of both AST and ALT of LZY228-treated group were lower than that of GA-treated group, indicating that LZY228 was a promising antitumor candidate. In addition, excellent in vivo antitumor potency of LZY228 was observed in MDA-MB-231 xenograft model, which was superior to reference drug 17-AAG. Docking and MD refinement of the Hsp90-LZY228 complex give us an explanation of theoretical binding model of 17-ferulamido-17-demethoxygeldanamycins at molecular level.

SUBMITTER: Li Z

PROVIDER: S-EPMC9076653 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Synthesis and biological evaluation of geldanamycin-ferulic acid conjugate as a potent Hsp90 inhibitor.

Li Zhenyu Z Jia Lejiao L Tang Hui H Shen Yuemao Y Shen Chengwu C

RSC advances 20191223 72

A novel geldanamycin-ferulic acid conjugate LZY228 was prepared and evaluated for anti-proliferation activity on human cancer cell line MDA-MB-231. Compound LZY228 exhibited potent cytotoxicity with IC<sub>50</sub> value of 0.27 μM, which was more potent than 17-AAG. Hepatotoxicity test in mice demonstrated that the levels of both AST and ALT of LZY228-treated group were lower than that of GA-treated group, indicating that LZY228 was a promising antitumor candidate. In addition, excellent <i>in ...[more]

PMID: 35542888

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