Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors

A novel series of triazoloquinazolinone derivatives were designed, synthesised, and evaluated for their in vitro biological activities against the SHP2 protein. Moreover, some compounds were evaluated against A375 cells. The results revealed that target compounds possessed moderate to excellent inhi...

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Autores principales:	Rongshuang Luo, Zhongyuan Wang, Dali Luo, Yumei Qin, Chunshen Zhao, Di Yang, Tian Lu, Zhixu Zhou, Zhuyan Huang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	triazoloquinazolinone derivatives shp2 inhibitors a375 cell line antitumor activity Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/f6b4e6f2b10c48e0b8e1d41569278350
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spelling	oai:doaj.org-article:f6b4e6f2b10c48e0b8e1d415692783502021-11-11T14:23:41ZDesign, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors1475-63661475-637410.1080/14756366.2021.1986491https://doaj.org/article/f6b4e6f2b10c48e0b8e1d415692783502021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/14756366.2021.1986491https://doaj.org/toc/1475-6366https://doaj.org/toc/1475-6374A novel series of triazoloquinazolinone derivatives were designed, synthesised, and evaluated for their in vitro biological activities against the SHP2 protein. Moreover, some compounds were evaluated against A375 cells. The results revealed that target compounds possessed moderate to excellent inhibitory activity against SHP2 protein, whereas compounds 12f, 12l, 12j, 17e, and 17f have strong antiproliferative activity on A375 cells. The compound 12l showed remarkable cytotoxicity against A375 cells and a strong inhibitory effect against SHP2 protein when compared with SHP244. The structure-activity relationships (SARs) indicated that electron-donating groups (EDGs) on phenyl rings are beneficial for improving the antitumor activity; compounds with a hydroxyl substituent at the 2-position of phenyl ring exhibited superior activities than compounds with a substituent at the 4-position. In addition, compound 12l displayed improved physicochemical properties as well as metabolic stability compared to SHP244. Our efforts identified 12l as a promising SHP2 protein inhibitor, warranting its further investigation.Rongshuang LuoZhongyuan WangDali LuoYumei QinChunshen ZhaoDi YangTian LuZhixu ZhouZhuyan HuangTaylor & Francis Grouparticletriazoloquinazolinone derivativesshp2 inhibitorsa375 cell lineantitumor activityTherapeutics. PharmacologyRM1-950ENJournal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 2170-2182 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	triazoloquinazolinone derivatives shp2 inhibitors a375 cell line antitumor activity Therapeutics. Pharmacology RM1-950
spellingShingle	triazoloquinazolinone derivatives shp2 inhibitors a375 cell line antitumor activity Therapeutics. Pharmacology RM1-950 Rongshuang Luo Zhongyuan Wang Dali Luo Yumei Qin Chunshen Zhao Di Yang Tian Lu Zhixu Zhou Zhuyan Huang Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors
description	A novel series of triazoloquinazolinone derivatives were designed, synthesised, and evaluated for their in vitro biological activities against the SHP2 protein. Moreover, some compounds were evaluated against A375 cells. The results revealed that target compounds possessed moderate to excellent inhibitory activity against SHP2 protein, whereas compounds 12f, 12l, 12j, 17e, and 17f have strong antiproliferative activity on A375 cells. The compound 12l showed remarkable cytotoxicity against A375 cells and a strong inhibitory effect against SHP2 protein when compared with SHP244. The structure-activity relationships (SARs) indicated that electron-donating groups (EDGs) on phenyl rings are beneficial for improving the antitumor activity; compounds with a hydroxyl substituent at the 2-position of phenyl ring exhibited superior activities than compounds with a substituent at the 4-position. In addition, compound 12l displayed improved physicochemical properties as well as metabolic stability compared to SHP244. Our efforts identified 12l as a promising SHP2 protein inhibitor, warranting its further investigation.
format	article
author	Rongshuang Luo Zhongyuan Wang Dali Luo Yumei Qin Chunshen Zhao Di Yang Tian Lu Zhixu Zhou Zhuyan Huang
author_facet	Rongshuang Luo Zhongyuan Wang Dali Luo Yumei Qin Chunshen Zhao Di Yang Tian Lu Zhixu Zhou Zhuyan Huang
author_sort	Rongshuang Luo
title	Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors
title_short	Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors
title_full	Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors
title_fullStr	Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors
title_full_unstemmed	Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors
title_sort	design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as shp2 protein inhibitors
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/f6b4e6f2b10c48e0b8e1d41569278350
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Design, synthesis, and biological evaluation of novel triazoloquinazolinone derivatives as SHP2 protein inhibitors

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