2. Academic Validation
  3. New modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment

New modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment

  • Bioorg Med Chem. 2020 Feb 15;28(4):115305. doi: 10.1016/j.bmc.2020.115305.
Yiming Xu 1,  Dewang Jing 2,  Dong Zhao 3,  Yongji Wu 4,  Lu Xing 3,  Haroon Ur Rashid 5,  Haodong Wang 2,  Lisheng Wang 6,  Huiling Cao 7
Affiliations

Affiliations

  • 1 Medicinal College, Guangxi University, Nanning 530004, China; School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
  • 2 School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.
  • 3 Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic Translational Medicine, Xi'an Medical University, Xi'an 710021, China.
  • 4 College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
  • 5 School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China; Department of Chemistry, Sarhad University of Science & Information Technology, Peshawar, Khyber Pakhtunkhwa 25120, Pakistan.
  • 6 Medicinal College, Guangxi University, Nanning 530004, China. Electronic address: [email protected].
  • 7 Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic Translational Medicine, Xi'an Medical University, Xi'an 710021, China. Electronic address: [email protected].
PMID: 31928863 DOI: 10.1016/j.bmc.2020.115305
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.

Keywords

Anticancer activity; L-shaped matrine derivatives; Mechanism of action; Radicicol; Thermal shift assay.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-150655
    Hsp90 Inhibitor
    HSP