Breast cancer resistant protein (BCRP/ABCG2), a 72 kDa plasma membrane transporter protein is a member of ABC transporter superfamily. Increased expression of BCRP causes increased efflux and therefore, reduced intracellular accumulation of many unrelated chemotherapeutic agents leading to multidrug resistance (MDR). A series of 31 benzamide and phenyltetrazole derivatives with amide and urea linkers has been synthesized to serve as potential BCRP inhibitors in order to overcome BCRP-mediated MDR. The target derivatives were tested for their cytotoxicity and reversal effects in human non-small cell lung cancer cell line H460 and mitoxantrone resistant cell line H460/MX20 using the MTT assay. In the benzamide series, compounds 6 and 7 exhibited a fold resistance of 1.51 and 1.62, respectively at 10 µM concentration which is similar to that of FTC, a known BCRP inhibitor. Compounds 27 and 31 were the most potent analogues in the phenyltetrazole series with amide linker with a fold resistance of 1.39 and 1.32, respectively at 10 µM concentration. For the phenyltetrazole series with urea linker, 38 exhibited a fold resistance of 1.51 which is similar than that of FTC and is the most potent compound in this series. The target compounds did not exhibit reversal effect in P-gp overexpressing resistant cell line SW620/Ad300 suggesting that they are selective BCRP inhibitors.

乳腺癌抗性蛋白（BCRP / ABCG2）是一种72 kDa的质膜转运蛋白，是ABC转运蛋白超家族的成员。BCRP表达增加导致外排增加，因此减少了许多不相关的化学治疗剂的细胞内积累，从而导致了多药耐药性（MDR）。为了克服BCRP介导的MDR，已合成了31种具有酰胺和脲连接基的苯甲酰胺和苯基四唑衍生物，用作潜在的BCRP抑制剂。使用MTT测定法测试了目标衍生物在人非小细胞肺癌细胞系H460和米托蒽醌抗性细胞系H460 / MX20中的细胞毒性和逆转作用。在苯甲酰胺系列中，化合物6和7在10 µM的浓度下，抗折叠性分别为1.51和1.62，这与已知的BCRP抑制剂FTC相似。化合物27和31是具有酰胺接头的苯基四唑系列中最有效的类似物，在10 µM浓度下的耐折叠性分别为1.39和1.32。对于具有脲连接基的苯基四唑系列，38的抗折叠性为1.51，与FTC相似，是该系列中最有效的化合物。目标化合物在过表达P-gp的耐药细胞系SW620 / Ad300中没有显示逆转作用，表明它们是选择性的BCRP抑制剂。