Abstract 4063: Design and synthesis of indole derivatives as ABCG2 mediated resistance reversal agents

Abstract

Abstract Multidrug resistance is a phenomenon that cancer cells become resistant to anticancer drugs. Multidrug resistance has been shown to be related with the overexpression of ATP-binding (ABC) transporters, including ABCG2. Therefore, ABCG2 is a therapeutic target for the development of multidrug resistance reversal agents. Fumitremorgin C, with an indole group which is an important pharmacophore in many drugs, is a known ABCG2 inhibitor. Inspired by this, we synthesized two series of indole derivatives as ABCG2 mediated resistance reversal agents. With MTT assay, we found that two compounds from the two series of indole derivatives respectively exhibited good reversal activity against ABCG2. The two compounds did not significantly alter the expression of ABCG2 in ABCG2-overexpressing cell lines and they stimulated the basal ATP hydrolysis of ABCG2. Citation Format: Chao-Yun Cai, Hong Zhai, Zi-Ning Lei, Bao-Li Chen, Zhao-Yi Du, Yun-Kai Zhang, Yi-Jun Wang, Bo Wang, Zhe-Sheng Chen. Design and synthesis of indole derivatives as ABCG2 mediated resistance reversal agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4063. doi:10.1158/1538-7445.AM2017-4063