苯磺酰胺类抑制剂与CAIX的结合机制  

The Binding Mechanism of Benzene Sulfonamide Inhibitors to Carbonic Anhydrase

作　　者：朱文友 张东华 李丹丹 庄文昌[1] 高美华 Zhu Wen-you;Zhang Dong-hua;Li Dan-dan;Zhuang Wen-chang;Gao Mei-hua

机构地区：[1]徐州工程学院材料与化学工程学院,江苏徐州221111

出　　处：《化工设计通讯》2022年第1期198-201,共4页Chemical Engineering Design Communications

基　　金：国家自然科学基金(21703194);徐州市科技创新专项基金(KC17080)。

摘　　要：碳酸酐酶IX(CAIX)是碳酸酐酶的一种异构酶,作用于细胞增殖和肿瘤的形成过程中,并且和肿瘤的乏氧代谢密切相关。以苯磺酰胺为母体构建了30种抑制剂分子,使用AutoDock4.2将30种抑制剂分子对接到CAIX的活性中心。结果表明:抑制剂分子氨基上的H与THR198上的O形成氢键,活动中心的金属离子Zn^(2+)与小分子、HIS93、HIS91、HIS117形成配位键,使抑制剂分子能够稳定在CAIX的活动中心。5、6、7、30号抑制剂分子与CAIX的结合最稳定,结合能分别是-7.31、-9.19、-9.86、-7.29 kcal/mol。Carbonic anhydrase IX(CAIX)is an isomerase of carbonic anhydrase(CA).Carbonic anhydrase CAIX plays an important role in the research of cancer treatment.In this study,carbonic anhydrase was designed as receptor protein,and benzenesulfonamide was used as the parent of construction inhibitor.Autodock 4.2 molecular docking program was used to dock 30 different inhibitors with carbonic anhydrase receptors.The results show that H on the amino group of the inhibitor forms hydrogen bond with O on thr198,and Zn^(2+)in the active center forms coordination bond with small molecule,His93,His91 and His117,which makes the inhibitor stable in the active center of carbonic anhydrase.The results showed that:5,6,7 and 30 were the most stable binding molecules with carbonic anhydrase,and the absolute values of binding energy were 7.31,9.19,9.86 and 7.29 kcal/mol,respectively.

关 键 词：碳酸酐酶 苯磺酰胺 抑制剂 分子对接 异构酶 

分 类 号：R914[医药卫生—药物化学]