Institute of Biology, Pedagogical University of Krakow, Podchorążych 2, 30-084 Kraków, Poland.
Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary.
Int J Mol Sci. 2022 Sep 16;23(18):10812. doi: 10.3390/ijms231810812.
Multidrug resistance (MDR) is considered one of the major mechanisms responsible for the failure of numerous anticancer and antiviral chemotherapies. Various strategies to overcome the MDR phenomenon have been developed, and one of the most attractive research directions is focused on the inhibition of MDR transporters, membrane proteins that extrude cytotoxic drugs from living cells. Here, we report the results of our studies on a series newly synthesized of 5-arylidenerhodanines and their ability to inhibit the ABCB1 efflux pump in mouse T-lymphoma cancer cells. In the series, compounds possessing a triphenylamine moiety and the carboxyl group in their structure were of particular interest. These amphiphilic compounds showed over 17-fold stronger efflux pump inhibitory effects than verapamil. The cytotoxic and antiproliferative effects of target rhodanines on T-lymphoma cells were also investigated. A putative binding mode for , one of the most potent P-gp inhibitors tested here, was predicted by molecular docking studies and discussed with regard to the binding mode of verapamil.
多药耐药性（MDR）被认为是导致许多抗癌和抗病毒化疗失败的主要机制之一。已经开发出各种克服 MDR 现象的策略，其中最有吸引力的研究方向之一是专注于抑制 MDR 转运蛋白，这些膜蛋白将细胞毒性药物从活细胞中排出。在这里，我们报告了一系列新合成的 5-芳亚基罗丹宁及其抑制 ABCB1 外排泵的能力的研究结果，这些化合物在结构中含有三苯胺部分和羧基。这些两亲性化合物对 ABCB1 外排泵的抑制作用比维拉帕米强 17 倍以上。还研究了目标罗丹宁对 T 淋巴瘤细胞的细胞毒性和抗增殖作用。通过分子对接研究预测了测试的最有效 P-糖蛋白抑制剂之一的可能结合模式，并结合维拉帕米的结合模式进行了讨论。
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