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聚腺苷二磷酸核糖聚合酶-1[poly(ADP-ribose)polymerase-1,PARP-1]能够催化ADP-核糖单元从烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD+)转移至受体蛋白,参与单链受损DNA的修复,是一种潜在的抗癌药物靶点。本文设计并合成了3-(2-氧代-2-取代)乙酰氨基苯甲酰胺类化合物16个,评价了所有目标化合物对PARP-1酶的抑制活性。其中6个化合物对PARP-1显示出了一定的抑制活性(0.23~5.78μmol·L-1)。初步探讨了该类化合物的构效关系,利用分子对接方法探索了目标化合物与PARP-1的作用模式,为进一步结构改造提供了依据。
Poly (ADP-ribose) polymerase-1, PARP-1] is able to catalyze the ADP-ribose sugar cell transfer from nicotinamide adenine dinucleotide (NAD +) to Somatic proteins, involved in the repair of single-stranded damaged DNA, are potential anticancer drug targets. In this paper, 16 compounds of 3- (2-oxo-2-substituted) acetamidobenzamides were designed and synthesized to evaluate the inhibitory activity of all the target compounds against PARP-1. Six compounds showed some inhibitory activity against PARP-1 (0.23 ~ 5.78μmol·L-1). The structure-activity relationship of these compounds was discussed preliminarily. The mode of interaction between the target compound and PARP-1 was explored by molecular docking method, which provided the basis for further structural transformation.