1610804-90-4Relevant articles and documents
Discovery of novel P-glycoprotein-mediated multidrug resistance inhibitors bearing triazole core via click chemistry
Liu, Baomin,Qiu, Qianqian,Zhao, Tianxiao,Jiao, Lei,Hou, Jianyu,Li, Yunman,Qian, Hai,Huang, Wenlong
, p. 182 - 191 (2014/07/22)
A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors bearing a triazol-phenethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity (IC50s > 100 μm). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo-sensitizing effect (>24 h) than VRP (6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P-gp-mediated MDR inhibitor.