萘查耳酮类 PTP1B 抑制剂的合成与活性研究  

SYNTHESIS AND ACTIVITY OF BENZO-CHALCONE DERIVATIVES AS PTP1B INHIBITORS

作　　者：施晓文 郭乔月 廖远峰 邓先清 SHI Xiao-wen;GUO Qiao-yue;LIAO Yuan-feng;DENG Xian-qing(Health Science Center,Jinggangshan University,Ji’an,Jiangxi,343009,China;Ji'an Science and Technology Innovation Development Center,Ji’an,Jiangxi 343000,China)

机构地区：[1]井冈山大学医学部,江西吉安343009 [2]吉安市科技创新发展中心,江西吉安343000

出　　处：《井冈山大学学报（自然科学版）》2024年第1期41-47,共7页Journal of Jinggangshan University (Natural Science)

基　　金：国家自然科学基金项目(21562028);吉安市2023年度指导性科技计划项目(吉市科计字(2023)6号)。

摘　　要：蛋白酪氨酸磷酸酯酶1B(PTP1B)作为非受体型PTPase家族成员之一,参与很多生理和病理过程的调控,尤其是对胰岛素信号通路中能量和葡萄糖稳态的调控,使其成为治疗糖尿病和肥胖症的新靶点。本研究基于PTP1B活性位点,利用计算机辅助药物设计方法,设计、合成了一系列羟基萘查尔酮及其环合衍生物(1a-1g,2a-2g),并评估了它们对PTP1B酶的抑制活性。本研究获得了4个活性较好的PTP1B抑制剂,IC_(50)分别为1.91、8.59、7.38、4.64μM,为开发具有良好细胞渗透性和生物利用度的新型PTP1B抑制剂提供了新的方向。Protein tyrosine phosphodiesterase 1B(PTP1B),a member of the non-receptor PTPase family,is involved in the regulation of many physiological and pathological processes,especially the regulation of energy and glucose homeostasis in the insulin signaling pathway.It has been identified as a potential therapeutic target for the treatment of diabetes and obesity.In this study,a series of hydroxy-contained benzo-chalcones and their cyclic derivatives(1a-1g,2a-2g)were designed and synthesized using computer-based drug design methodology based on the PTP1B active site.And their inhibitory activity against PTP1B enzyme was evaluated.In the present study,four active PTP1B inhibitors were obtained with IC_(50) values of 1.91,8.59,7.38,and 4.64μM,respectively.This study provides a new direction for the development of novel PTP1B inhibitors with good cell permeability and bioavailability.

关 键 词：糖尿病 肥胖症 萘查尔酮 PTP1B 抑制剂 

分 类 号：O625.32[理学—有机化学]