The Breast Cancer Resistance Protein (BCRP/ABCG2) belongs to the G class of ABC (ATP-Binding Cassette) proteins, which is known as one of the main transporters involved in the multidrug resistance (MDR) phenotype that confer resistance to anticancer drugs. The aim of this study was to design, synthesize and develop new potent and selective inhibitors of BCRP that can be used to abolish MDR and potentialize clinically used anticancer agents. In previous reports, we showed the importance of chromone scaffold and hydrophobicity for the inhibition of ABC transporters. In the present study we report the design and development of chromones linked to one or two amino acids residues that are either hydrophobic or found in the structure of FTC, one of most potent (but highly toxic) inhibitors of BCRP. Herewith, we report the synthesis and evaluation of 13 compounds. The studied molecules were found to be not toxic and showed strong inhibition activity as well as high selectivity toward BCRP. The highest activity was obtained with the chromone bearing a valine residue (9c) which showed an inhibition activity against BCRP of 50 nM. The rationalization of the inhibition potential of the most active derivatives was performed through docking studies. Taken together, the ease of synthesis and the biological profile of these compounds render them as promising candidates for further development in the field of anticancer therapy.

乳腺癌抗性蛋白（BCRP / ABCG2）属于G类ABC（ATP结合盒式磁带）蛋白，它是涉及多药耐药性（MDR）表型的主要转运蛋白之一，赋予抗癌药耐药性。这项研究的目的是设计，合成和开发新的有效和选择性的BCRP抑制剂，可用于废除MDR并潜在地开发临床使用的抗癌剂。在以前的报告中，我们显示了色酮支架和疏水性对于抑制ABC转运蛋白的重要性。在本研究中，我们报告了与一或两个氨基酸残基相关的色酮的设计和开发，这些残基要么是疏水的，要么是FTC的结构之一，FTC是最有效（但毒性很高）的BCRP抑制剂之一。因此，我们报告了13种化合物的合成和评估。发现所研究的分子无毒并且显示出强的抑制活性以及对BCRP的高选择性。带有缬氨酸残基的色酮具有最高的活性（图9c）显示出对BCRP的抑制活性为50nM。通过对接研究对活性最高的衍生物的抑制潜力进行了合理化。综上所述，这些化合物的合成容易性和生物学特性使其成为抗癌治疗领域进一步发展的有希望的候选者。