2. Academic Validation
  3. Quantitative Structure⁻Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells

Quantitative Structure⁻Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells

  • Molecules. 2019 Apr 27;24(9):1661. doi: 10.3390/molecules24091661.
Mengmeng Xia 1,  Yajing Fang 2,  Weiwei Cao 3,  Fuqiang Liang 4,  Siyi Pan 5,  Xiaoyun Xu 6
Affiliations

Affiliations

  • 1 Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China. xiamengmeng@webmail.hzau.edu.cn.
  • 2 Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China. fyj@webmail.hzau.edu.cn.
  • 3 Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China. weiweicao@webmail.hzau.edu.cn.
  • 4 Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China. lfqzyw@webmail.hzau.edu.cn.
  • 5 Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China. Pansiyi@mail.hzau.edu.cn.
  • 6 Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China. xuxiaoyun@mail.hzau.edu.cn.
PMID: 31035631 DOI: 10.3390/molecules24091661
Abstract

P-glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance (MDR) in Cancer cells. In order to enhance the uptake of chemotherapy drugs, larger amounts of P-gp inhibitors are required. Besides several chemically synthesized P-gp inhibitors, Flavonoids as P-gp inhibitors are being investigated, with their advantages including abundance in our daily diet and a low toxicity. The cytotoxicity of daunorubicin (as a substrate of P-gp) to KB/MDR1 cells and the parental KB cells was measured in the presence or absence of Flavonoids. A two-dimensional quantitative structure-activity relationship (2D-QSAR) model was built with a high cross-validation coefficient (Q2) value of 0.829. Descriptors including vsurf_DW23, E_sol, Dipole and vsurf_G were determined to be related to the inhibitory activity of Flavonoids. The lack of 2,3-double bond, 3'-OH, 4'-OH and the increased number of methoxylated substitutions were shown to be beneficial for the inhibition of P-gp. These results are important for the screening of Flavonoids for inhibitory activity on P-gp.

Keywords

P-gp; QSAR; flavonoids; inhibitory activity.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z