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New modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment.
Bioorg Med Chem ; 28(4): 115305, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31928863
ABSTRACT
The similarity of spatial structure between radicicol and matrine urged us to perform conformation modification of matrine, followed by L-shaped matrine derivatives, 6, 12, 21a-h and 22a-h were originally designed, synthesized and evaluated for Hsp90N inhibitors as anticancer agents. TSA (Thermal Shift Assay) results indicated that 21e, 22a-c and 22e-g exhibited strong binding force against Hsp90N with∣ΔTm∣ > 3, meanwhile, MTT assay also revealed these compounds displayed potent anticancer activity with IC50 values below 25 µM against HepG2, HeLa and MDA-MB-231 cells lines. Then, compound 22g with a high ΔTm = 10.92 was chosen as a representative to perform further mechanism study. It can induce cell apoptosis, arrest the cell cycle at the S phase and decrease the expression level of Hsp90 in Hela cell. These results originally provided targeted modification strategy for matrine derivatives to serve as Hsp90 inhibitors for cancer therapy.

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: Bioorg Med Chem Assunto da revista: Bioquímica / Química Ano de publicação: 2020 Tipo de documento: Artigo País de afiliação: China