In this study, a new series of heterodimers was synthesized. These derivatives are N,N-bis(alkanol)amine aryl esters or N,N-bis(ethoxyethanol)amine aryl esters carrying a methoxylated aryl residue combined with a flavone or chromone moiety. The new compounds were studied to evaluate their P-gp modulating activity on a multidrug-resistant leukemia cell line. Some of the new compounds show a good MDR reversing activity; interestingly this new series of compounds does not comply with the structure-activity relationships (SAR) outlined by previously synthesized analogs carrying different aromatic moieties. In the case of the compounds described in this paper, activity is linked to different features, in particular the characteristics of the spacer, which seem to be critical for the interaction with the pump. This fact indicates that the presence of a flavone or chromone residue influences the SAR of these series of products, and that flexible molecules can find different productive binding modes with the P-gp recognition site. These results support the synthesis of new compounds that might be useful leads for the development of drugs to control P-gp-dependent MDR.

在这项研究中，合成了一系列新的异二聚体。这些衍生物是Ñ，ñ -双（链烷醇）胺的芳基的酯或Ñ，ñ -带有甲氧基化的芳基残基与黄酮或色酮部分结合的双（乙氧基乙醇）胺芳基酯。研究了这些新化合物，以评估其对多药耐药性白血病细胞系的P-gp调节活性。一些新化合物显示出良好的MDR逆转活性。有趣的是，该系列新化合物不符合先前合成的带有不同芳族部分的类似物所概述的结构-活性关系（SAR）。对于本文所述的化合物，活性与不同的特征相关，尤其是垫片的特征，这对于与泵的相互作用似乎至关重要。这一事实表明，黄酮或色酮残基的存在会影响这些系列产品的SAR，而且柔性分子可以通过P-gp识别位点找到不同的生产性结合模式。这些结果支持了新化合物的合成，这可能是开发控制P-gp依赖性MDR的药物的有用线索。