Discovery of Potent Inhibitors against P-Glycoprotein-Mediated Multidrug Resistance Aided by Late-Stage Functionalization of a 2-(4-(Pyridin-2-yl)phenoxy)pyridine Analogue
Yao Ma, Da-Wei Yin, Jingjia Ye, Xiduan Wei, Yameng Pei, Xueyuan Li, Guangxu Si, Xuan-Yu Chen, Zhe‐Sheng Chen, Yi Dong, Feng Zou, Wei Shi, Qianqian Qiu, Hai Qian, Gang Liu
Abstract
SIS3 is a specific inhibitor of Smad3 that inhibits the TGFβ1-induced phosphorylation of Smad3. In this article, a variety of SIS3 derivatives were designed and synthesized to discover potential inhibitors against P-glycoprotein-mediated multidrug resistance aided by late-stage functionalization of a 2-(4-(pyridin-2-yl)phenoxy)pyridine analogue. A novel class of potent P-gp reversal agents were investigated, and a lead compound 37 was identified as a potent P-gp reversal agent with strong bioactivity and outstanding affinity for P-gp.
Topics & Concepts
ChemistryMultiple drug resistanceP-glycoproteinPyridineSurface modificationStereochemistryGlycoproteinPharmacologyBiochemistryMedicinal chemistryBiologyAntibioticsPhysical chemistryDrug Transport and Resistance MechanismsOral and gingival health researchDiabetes Treatment and Management