Abstract

ABSTRCT

A series of novel triazoloquinolinone and imidazoquinazolinone derivatives were designed and synthesised, and their biological activities against SHP2 protein and melanoma A357 cell line were evaluated in vitro. The results show that some target compounds have moderate to excellent inhibitory activity on SHP2 protein and melanoma A357 cell line. Structure-activity relationships (SARs) showed that both imidazoquinazolinone and triazoloquinazolinone derivatives have good SHP2 protein kinase and melanoma cell line A357 inhibitory activity. The results of molecular docking also showed that the cores of imidazoquinazolinone and triazoloquinazolinone have a certain affinity for SHP2 protein at the same time. Compared with SHP244, the target compounds have quite good liver microsomal stability and has more drug potential. The most promising compound B1 has a strong inhibitory effect on the melanoma cell line A357 at 100 µM (76.15% inhibition).

Details

Title
Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase
Author
Ye, Wenjun 1 ; Liu, Ye 1 ; Ren, Qian 1 ; Liao, Tianhui 1 ; Chen, Yumei 1 ; Chen, Dongmei 1 ; Wang, Sisi 1 ; Yao, Lihong 1 ; Jia, Yihe 2 ; Zhao, Chunshen 1 ; Zhou, Zhixu 1 

 School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;; Guizhou Engineering Laboratory for Synthetic Drugs, Guiyang, China; 
 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China 
Pages
1495-1513
Publication year
2022
Publication date
Dec 2022
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2727915986
Copyright
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.