Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors

Peptidyl-prolyl <i>cis/trans</i> isomerase Pin1 plays a key role in amplifying and translating multiple oncogenic signaling pathways during oncogenesis. The blockade of Pin1 provided a unique way of disrupting multiple oncogenic pathways and inducing apoptosis. Aiming to develop potent P...

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Main Authors:	Shuxiang Wang, Lihong Guan, Jie Zang, Kun Xing, Jian Zhang, Dan Liu, Linxiang Zhao
Format:	Article
Language:	English
Published:	MDPI AG 2019-03-01
Series:	Molecules
Subjects:	Pin1 inhibitors benzimidazole derivatives antiproliferative activity
Online Access:	https://www.mdpi.com/1420-3049/24/7/1198

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spelling	doaj-933447aac5ab451a9e3a759afb3fbe4e2020-11-24T20:42:10ZengMDPI AGMolecules1420-30492019-03-01247119810.3390/molecules24071198molecules24071198Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 InhibitorsShuxiang Wang0Lihong Guan1Jie Zang2Kun Xing3Jian Zhang4Dan Liu5Linxiang Zhao6Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaPeptidyl-prolyl <i>cis/trans</i> isomerase Pin1 plays a key role in amplifying and translating multiple oncogenic signaling pathways during oncogenesis. The blockade of Pin1 provided a unique way of disrupting multiple oncogenic pathways and inducing apoptosis. Aiming to develop potent Pin1 inhibitors, a series of benzimidazole derivatives were designed and synthesized. Among the derivatives, compounds <b>6h</b> and <b>13g</b> showed the most potent Pin1 inhibitory activity with IC<sub>50</sub> values of 0.64 and 0.37 μM, respectively. In vitro antiproliferative assay demonstrated that compounds <b>6d</b>, <b>6g</b>, <b>6h</b>, <b>6n</b>, <b>6o</b> and <b>7c</b> exhibited moderate antiproliferative activity against human prostate cancer PC-3 cells. Taken together, these unique benzimidazole derivatives exhibited great potential to be further explored as potent Pin1 inhibitors with improved potency.https://www.mdpi.com/1420-3049/24/7/1198Pin1 inhibitorsbenzimidazole derivativesantiproliferative activity
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Shuxiang Wang Lihong Guan Jie Zang Kun Xing Jian Zhang Dan Liu Linxiang Zhao
spellingShingle	Shuxiang Wang Lihong Guan Jie Zang Kun Xing Jian Zhang Dan Liu Linxiang Zhao Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors Molecules Pin1 inhibitors benzimidazole derivatives antiproliferative activity
author_facet	Shuxiang Wang Lihong Guan Jie Zang Kun Xing Jian Zhang Dan Liu Linxiang Zhao
author_sort	Shuxiang Wang
title	Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors
title_short	Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors
title_full	Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors
title_fullStr	Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors
title_full_unstemmed	Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors
title_sort	structure-based design of novel benzimidazole derivatives as pin1 inhibitors
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2019-03-01
description	Peptidyl-prolyl <i>cis/trans</i> isomerase Pin1 plays a key role in amplifying and translating multiple oncogenic signaling pathways during oncogenesis. The blockade of Pin1 provided a unique way of disrupting multiple oncogenic pathways and inducing apoptosis. Aiming to develop potent Pin1 inhibitors, a series of benzimidazole derivatives were designed and synthesized. Among the derivatives, compounds <b>6h</b> and <b>13g</b> showed the most potent Pin1 inhibitory activity with IC<sub>50</sub> values of 0.64 and 0.37 μM, respectively. In vitro antiproliferative assay demonstrated that compounds <b>6d</b>, <b>6g</b>, <b>6h</b>, <b>6n</b>, <b>6o</b> and <b>7c</b> exhibited moderate antiproliferative activity against human prostate cancer PC-3 cells. Taken together, these unique benzimidazole derivatives exhibited great potential to be further explored as potent Pin1 inhibitors with improved potency.
topic	Pin1 inhibitors benzimidazole derivatives antiproliferative activity
url	https://www.mdpi.com/1420-3049/24/7/1198
work_keys_str_mv	AT shuxiangwang structurebaseddesignofnovelbenzimidazolederivativesaspin1inhibitors AT lihongguan structurebaseddesignofnovelbenzimidazolederivativesaspin1inhibitors AT jiezang structurebaseddesignofnovelbenzimidazolederivativesaspin1inhibitors AT kunxing structurebaseddesignofnovelbenzimidazolederivativesaspin1inhibitors AT jianzhang structurebaseddesignofnovelbenzimidazolederivativesaspin1inhibitors AT danliu structurebaseddesignofnovelbenzimidazolederivativesaspin1inhibitors AT linxiangzhao structurebaseddesignofnovelbenzimidazolederivativesaspin1inhibitors
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Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors

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