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Discovery of Novel P‐Glycoprotein‐Mediated Multidrug Resistance Inhibitors Bearing Triazole Core via Click Chemistry
Author(s) -
Liu Baomin,
Qiu Qianqian,
Zhao Tianxiao,
Jiao Lei,
Hou Jianyu,
Li Yunman,
Qian Hai,
Huang Wenlong
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12301
Subject(s) - p glycoprotein , multiple drug resistance , cytotoxicity , chemistry , click chemistry , tetrahydroisoquinoline , verapamil , triazole , potency , pharmacology , in vitro , stereochemistry , biochemistry , combinatorial chemistry , biology , antibiotics , organic chemistry , calcium
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 ( IC 50 s > 100 μ m ). Compared with VRP , compound 5 exhibited more potency in increasing drug accumulation in K 562/ A 02 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.
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