| 施晓文,郭乔月,廖远峰,邓先清.萘查耳酮类PTP1B抑制剂的合成与活性研究[J].井冈山大学自然版,2024,45(1):41-47 |
| 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 |
| 投稿时间：2023-09-20 修订日期：2023-12-06 |
| DOI：10.3969/j.issn.1674-8085.2024.01.001 |
| 中文关键词: 糖尿病 肥胖症 萘查尔酮 PTP1B 抑制剂 |
| 英文关键词: diabetes obesity benzo-chalcone PTP1B inhibitor |
| 基金项目: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) |
| 作者 | 单位 | | 施晓文 | 井冈山大学医学部, 江西, 吉安 343009
吉安市科技创新发展中心, 江西, 吉安 343000 | | 郭乔月 | 井冈山大学医学部, 江西, 吉安 343009 | | 廖远峰 | 井冈山大学医学部, 江西, 吉安 343009 | | 邓先清 | 井冈山大学医学部, 江西, 吉安 343009 |
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| 中文摘要: |
| 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，IC50分别为1.91、8.59、7.38、4.64 μM，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。 |
| 英文摘要: |
| 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 IC50 values of 1.91, 8.59, 7.38, and 4.64 μM, respectively. This study provides a new direction for the development of novel PTP1B inhibitors with good cell permeability and bioavailability. |
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