2. Academic Validation
  3. neo-Clerodane diterpenoids from Scutellaria barbata mediated inhibition of P-glycoprotein in MCF-7/ADR cells

neo-Clerodane diterpenoids from Scutellaria barbata mediated inhibition of P-glycoprotein in MCF-7/ADR cells

  • Eur J Med Chem. 2016 Oct 4:121:238-249. doi: 10.1016/j.ejmech.2016.05.045.
Gui-Min Xue 1,  Yuan-Zheng Xia 1,  Zhi-Min Wang 1,  Ling-Nan Li 1,  Jian-Guang Luo 2,  Ling-Yi Kong 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
  • 2 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: luojg@cpu.edu.cn.
  • 3 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: cpu_lykong@126.com.
PMID: 27240278 DOI: 10.1016/j.ejmech.2016.05.045
Abstract

Ten new (1-10) and seventeen known (11-27) neo-clerodane Diterpenoids substituted with nicotinoyloxyl were isolated from the plant Scutellaria barbata and their structures were established by extensive spectroscopic analysis. Chemoreversal effects of these neo-clerodane Diterpenoids on multidrug resistance were evaluated in breast Cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein. Four compounds (11, 14, 16, and 18) exhibited better chemoreversal abilities than the classical P-gp inhibitor verapamil and the most potent compound 11 reduced IC50 value of adriamycin in MCF-7/ADR cells from 58.8 μM to 1.3 μM. Mechanistic investigations showed that compound 11 reversed multidrug resistance through suppressing the activity of P-gp and restraining the expression of P-glycoprotein. In the present study, the structure-activity relationships of neo-clerodane Diterpenoids were also discussed.

Keywords

Multidrug resistance; P-glycoprotein; Scutellaria barbata; Structure–activity relationship; neo-Clerodane diterpenoid.

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