Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
In Vivo. 2012 Mar-Apr;26(2):293-7.
Multidrug resistance (MDR) is one of the major concerns in the treatment of cancer and one of the major causes of therapy failure. The overexpression of an ABC transporter, the ABCB1, is often associated with MDR in cancer. Previously it was observed that hydantoin compounds can modulate the activity of the ABCB1 pump.
Fourteen hydantoin derivatives were synthesized and studied for their capacity to increase accumulation of ethidium bromide (EB) by mouse lymphoma cancer cells that were transfected with the human ABCB1 gene and overexpress the human ABCB1 pump.
It was observed that the accumulation of EB by the cells in the presence of four of the newly synthesized hydantoins was strongly increased. Similar but milder effects were also observed for the other seven hydantoins; the remaining three had no activity.
The 14 hydantoin compounds studied belong to three different structural groups. Structure-activity relationships were studied and important molecular substituents that were possibly responsible for increased the activity of the molecules were identified. This important information may lead to the continuation of our work and to the future synthesis of more active compounds.
多药耐药性（MDR）是癌症治疗中的主要关注点之一，也是治疗失败的主要原因之一。ABC 转运蛋白的过度表达通常与癌症中的 MDR 有关。先前观察到，海因衍生物可以调节 ABCB1 泵的活性。
合成了 14 种海因衍生物，并研究了它们增加转染人 ABCB1 基因并过表达人 ABCB1 泵的小鼠淋巴瘤癌细胞中溴化乙锭（EB）积累的能力。
观察到在四种新合成的海因的存在下，细胞中 EB 的积累明显增加。另外七种海因也观察到类似但较温和的作用；其余三种没有活性。
研究的 14 种海因化合物属于三个不同的结构群。研究了构效关系，并确定了可能导致分子活性增加的重要分子取代基。这些重要信息可能会导致我们继续我们的工作，并合成更具活性的化合物。
