New modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment
Copyright policy )New modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment
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.
- Xi'an Medical University China (People's Republic of)
- Guangxi University China (People's Republic of)
- Sarhad University of Science and Information Technology Pakistan
- Sarhad University of Science & IT, Ring Road (Hayatabad Link) Peshawar Pakistan
- North University of China China (People's Republic of)
Dose-Response Relationship, Drug, Molecular Conformation, Antineoplastic Agents, Apoptosis, Molecular Docking Simulation, Structure-Activity Relationship, Alkaloids, Cell Line, Tumor, Humans, HSP90 Heat-Shock Proteins, Drug Screening Assays, Antitumor, Matrines, Quinolizines, Cell Proliferation
Dose-Response Relationship, Drug, Molecular Conformation, Antineoplastic Agents, Apoptosis, Molecular Docking Simulation, Structure-Activity Relationship, Alkaloids, Cell Line, Tumor, Humans, HSP90 Heat-Shock Proteins, Drug Screening Assays, Antitumor, Matrines, Quinolizines, Cell Proliferation
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