In this section, you can access to the latest technical information related to the FUTURE project topic.

Design, synthesis and biological evaluation of novel phenylfuran-bisamide derivatives as P-glycoprotein inhibitors against multidrug resistance in MCF-7/ADR cell

The co-administration of anticancer drugs and P-glycoprotein (P-gp) inhibitors was a treatment strategy to surmount multidrug resistance (MDR) in anticancer chemotherapy. In this study, novel phenylfuran-bisamide derivatives were designed as P-gp inhibitors based on target-based drug design, and 31 novel compounds were synthesized and screened on MCF-7/ADR cells. The result of bioassay revealed that compound y12d exhibited low cytotoxicity and promising MDR reversal activity (IC50?=?0.0320??M, reversal fold?=?1163.0), 3.64-fold better than third-generation P-gp inhibitor tariquidar (IC50?=?0.1165??M, reversal fold?=?319.3). The results of Western blot and rhodamine 123 accumulation verified that compound y12d exhibited excellent MDR reversal activity by inhibiting the efflux function of P-gp but not expression. Furthermore, molecular docking showed that compound y12d bound to target P-gp by forming the double H-bond interactions with residue Gln 725. These results suggest that compound y12d might be a potential MDR reveal agent acting as a P-gp inhibitor in clinical therapeutics, and provide insight into design strategy and skeleton optimization for the development of P-gp inhibitors.

» Author: Zhikun Yang, Xue Yang, Yasheng Li, Yue Cai, Yanlei Yu, Wenya Zhuang, Xuanrong Sun, Qingyong Li, Xiaoze Bao, Xinyi Ye, Jinmiao Tian, Bin Wei, Jianwei Chen, Qihao Wu, Huawei Zhang, Xiaozhou Mou, Hong Wang

» Publication Date: 15/02/2023

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