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Design, synthesis and evaluation of a novel series of inhibitors reversing P‐glycoprotein‐mediated multidrug resistance
Author(s) -
Ghaleb Hesham,
Li Huilan,
Kairuki Mutta,
Qiu Qianqian,
Bi Xinzhou,
Liu Chunxia,
Liao Chen,
Li Jieming,
Hezam Kamal,
Huang Wenlong,
Qian Hai
Publication year - 2018
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.13338
Subject(s) - p glycoprotein , multiple drug resistance , efflux , verapamil , pharmacology , doxorubicin , chemistry , cytotoxic t cell , drug resistance , chemotherapy , medicine , biochemistry , biology , in vitro , organic chemistry , microbiology and biotechnology , calcium , antibiotics
Multidrug resistance ( MDR ) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo‐reversal agents is needed to overcome MDR . Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil ( VRP ) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells. Compound 19 also played an important role in the P‐gp efflux function of intracellular Rh123 and doxorubicin ( DOX ) accumulation in K562/A02 cells. Moreover, compound 19 exhibited a long lifetime of approximately 24 hr. These results indicated that compound 19 is a potential lead compound for the design of new drugs to overcome cancer MDR .