Discovery and optimization of novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides as bifunctional antidiabetic agents stimulating both insulin secretion and glucose uptake
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jo, Jeyun | - |
dc.contributor.author | Lee, Dahae | - |
dc.contributor.author | Park, Yeong Hye | - |
dc.contributor.author | Choi, Hyeonjin | - |
dc.contributor.author | Han, Jinhee | - |
dc.contributor.author | Park, Do Hwi | - |
dc.contributor.author | Choi, You-Kyung | - |
dc.contributor.author | Kwak, Jinsook | - |
dc.contributor.author | Yang, Min-Kyu | - |
dc.contributor.author | Yoo, Jin-Wook | - |
dc.contributor.author | Moon, Hyung Ryong | - |
dc.contributor.author | Geum, Dongho | - |
dc.contributor.author | Kang, Ki Sung | - |
dc.contributor.author | Yun, Hwayoung | - |
dc.date.accessioned | 2021-11-19T23:41:04Z | - |
dc.date.available | 2021-11-19T23:41:04Z | - |
dc.date.created | 2021-08-30 | - |
dc.date.issued | 2021-05-05 | - |
dc.identifier.issn | 0223-5234 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/128052 | - |
dc.description.abstract | A novel series of 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides was designed, synthesized and evaluated for their biological activities on glucose-stimulated insulin secretion (GSIS). The cytotoxicity of all 41 novel compounds was screened to assess their pharmacological safety in pancreatic b-cells. A two-step optimization process was carried out to establish the structure-activity relationship for this class and subsequently we identified the most active analogue 26. Further modification study of 26 evidenced the necessity of N-hydrogens in the core architecture. Protein expression analysis suggested that 26 increases insulin secretion via the activation of the upstream effector of pancreatic and duodenal homeobox 1 (PDX-1), which is an important factor promoting GSIS. Moreover, the administration of 26 effectively augmented glucose uptake in C2C12 myotube cells via the suppression of Mitsugumin 53 (MG53), an insulin receptor substrate 1 (IRS-1) ubiquitination E3 ligase. (C) 2021 Elsevier Masson SAS. All rights reserved. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | - |
dc.subject | PANCREATIC BETA-CELLS | - |
dc.subject | PROTEIN-COUPLED RECEPTORS | - |
dc.subject | EXPRESSION | - |
dc.subject | RESISTANCE | - |
dc.title | Discovery and optimization of novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides as bifunctional antidiabetic agents stimulating both insulin secretion and glucose uptake | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Geum, Dongho | - |
dc.identifier.doi | 10.1016/j.ejmech.2021.113325 | - |
dc.identifier.scopusid | 2-s2.0-85103330765 | - |
dc.identifier.wosid | 000643683200003 | - |
dc.identifier.bibliographicCitation | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.217 | - |
dc.relation.isPartOf | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.title | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 217 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.subject.keywordPlus | PANCREATIC BETA-CELLS | - |
dc.subject.keywordPlus | PROTEIN-COUPLED RECEPTORS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordAuthor | Type 2 diabetes mellitus (T2DM) | - |
dc.subject.keywordAuthor | 3-Benzyl-N-phenyl-1H-pyrazole-5carboxamide | - |
dc.subject.keywordAuthor | Glucose-stimulated insulin secretion (GSIS) | - |
dc.subject.keywordAuthor | Glucose stimulation index (GSI) | - |
dc.subject.keywordAuthor | Structure-activity relationship (SAR) | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.