1. Exploration of 1,2,3-triazole-pyrimidine hybrids as potent reversal agents against ABCB1-mediated multidrug resistance.
- Author
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Wang B, Zhao B, Chen ZS, Pang LP, Zhao YD, Guo Q, Zhang XH, Liu Y, Liu GY, Hao-Zhang, Zhang XY, Ma LY, and Liu HM
- Subjects
- ATP Binding Cassette Transporter, Subfamily B antagonists & inhibitors, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Molecular Structure, Pyrimidines chemistry, Structure-Activity Relationship, Triazoles chemistry, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Drug Resistance, Neoplasm drug effects, Pyrimidines pharmacology, Triazoles pharmacology
- Abstract
ABCB1-mediated multidrug resistance (MDR) is a principal obstacle for successful cancer chemotherapy. A series of pyrimidine-based hybrid molecules containing 1,2,3-triazole moiety were evaluated for their reversal activities against MDR. The majority of target compounds displayed moderate to great reversal potency. Among these compounds, compound 25 displayed the most potent reversal activity, about 7-fold more potent than Verapamil (VRP). Further mechanism studies revealed that compound 25 could obviously reverse paclitaxel (PTX) resistance in SW620/AD300 cells by increasing accumulation and extending maintenance of PTX. Our findings indicate that the 1,2,3-triazole-pyrimidine-based derivatives may serve as an interesting lead for the development of new potent and efficacious ABCB1-dependent MDR modulators., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2018
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