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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells.
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Anti-calmodulin acridone derivatives modulate vinblastine resistance in multidrug resistant (MDR) cancer cells.

机译：抗钙调蛋白a啶酮衍生物可调节多药耐药（MDR）癌细胞中的长春碱耐药性。

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摘要

Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumors. Parent acridones 1A and 1B were prepared by the Ullmann reaction followed by cyclization and N-alkylation. N-(omega-Chloroalkyl) analogues were subjected to iodide catalyzed nucleophilic substitution reaction with secondary amines to get the compounds 3A-13A and 3B-13B, which enhanced the uptake of vinblastine in KBChR-8-5 cells to a greater extent (2.6-13.1-fold relative to control) than verapamil. The study on the structure-activity relationship revealed that substitution of -H at position C-4 in acridone nucleus by -OCH3 increased the cytotoxic and anti-MDR activities. The ability of acridones to inhibit calmodulin dependent cyclic AMP phosphodiesterase has been determined and the results have shown a strong positive correlation between anti-calmodulin activity and cytotoxicity in KBChR-8-5 cells or anti-MDR activity.
机译：多药耐药性（MDR）是限制化学疗法治疗肿瘤功效的主要障碍之一。通过Ullmann反应，然后环化和N-烷基化制备亲本a啶1A和1B。使N-（ω-氯代烷基）类似物与仲胺进行碘化物催化的亲核取代反应，得到化合物3A-13A和3B-13B，这在更大程度上增强了长春碱在KBChR-8-5细胞中的摄取（2.6相对于对照为-13.1倍）。对结构-活性关系的研究表明，-OCH3取代a啶酮核中C-4位的-H可以增加细胞毒性和抗MDR活性。已确定了cri啶酮抑制钙调蛋白依赖性环状AMP磷酸二酯酶的能力，结果表明抗钙调蛋白活性与KBChR-8-5细胞的细胞毒性或抗MDR活性之间具有很强的正相关性。

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