دورية أكاديمية
Design, Synthesis, and the Effects of ( E )-9-Oxooctadec-10-en-12-ynoic Acid Analogues to Promote Glucose Uptake.
| العنوان: | Design, Synthesis, and the Effects of ( E )-9-Oxooctadec-10-en-12-ynoic Acid Analogues to Promote Glucose Uptake. |
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| المؤلفون: | Kshirsagar RR; Centre for Organic and Medicinal Chemistry, Department of Chemistry, School of Advanced Sciences, VIT University, Vellore, Tamil Nadu 632014, India.; Discovery Analytical Sciences Department, Piramal Enterprises Limited, 1A - Nirlon Complex, Off Western Express Highway, Goregaon (East), Mumbai, Maharashtra 400 063, India., Gadekar PK; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Khedkar VM; Department of Pharmaceutical Chemistry, School of Pharmacy, Vishwakarma University, Pune, Maharashtra 411 048, India., Vijayakumar V; Centre for Organic and Medicinal Chemistry, Department of Chemistry, School of Advanced Sciences, VIT University, Vellore, Tamil Nadu 632014, India. |
| المصدر: | ACS omega [ACS Omega] 2021 Sep 09; Vol. 6 (37), pp. 24118-24127. Date of Electronic Publication: 2021 Sep 09 (Print Publication: 2021). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101691658 Publication Model: eCollection Cited Medium: Internet ISSN: 2470-1343 (Electronic) Linking ISSN: 24701343 NLM ISO Abbreviation: ACS Omega Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society, [2016]- |
| مستخلص: | ( E ) - 9-Oxooctadec-10-en-12-ynoic acid is found to mediate its antidiabetic activity by increasing insulin-stimulated glucose uptake in L6 myotubes by activating the phosphoinositide 3-kinase (PI3K) pathway. A simultaneous study of site-specific modification followed by structure-activity relationship provides a tremendous scope for exploiting the bioactivity of the parent molecule. Therefore, in the present study, we focused on site-specific modification of ( E ) - 9-oxooctadec-10-en-12-ynoic acid ( 1 ) to generate multiple derivatives and extensive structure-activity relationship (SAR) studies. We have done structural base design and synthesized a series of amides from acid compound 1 . Compound 1 consists of an acid functionality, which is known for its metabolism-related liabilities. The SAR has been generated using scaffolds of different antidiabetic drugs such as biguanides, sulfonylureas, thiazolidinediones/glitazones, peroxisome proliferator-activated receptors, K + ATP, α-glucosidase inhibitors, and others. Furthermore, the study demonstrates and explains the promising derivatives and importance of SAR of the compound ( E ) - 9-oxooctadec-10-en-12-ynoic acid. In order to gain mechanistic insights, a molecular docking study was performed against PI3K, which could identify the binding modes and thermodynamic interactions governing the binding affinity. According to our research, compounds 5 , 6 , 27 , 28 , 31 , 32 , and 33 are the best compounds from the series having EC Competing Interests: The authors declare no competing financial interest. (© 2021 The Authors. Published by American Chemical Society.) |
| References: | Mol Cell. 2000 Oct;6(4):909-19. (PMID: 11090628) ChemMedChem. 2013 Mar;8(3):385-95. (PMID: 23361977) Pharmacogn Rev. 2012 Jan;6(11):22-8. (PMID: 22654401) J Med Chem. 2004 Mar 25;47(7):1739-49. (PMID: 15027865) Eur J Med Chem. 2016 Oct 21;122:475-487. (PMID: 27423637) Bioorg Chem. 2019 May;86:507-512. (PMID: 30776681) Life Sci. 2016 May 15;153:100-17. (PMID: 27091376) AAPS J. 2008;10(1):178-92. (PMID: 18446518) Fitoterapia. 2016 Oct;114:26-33. (PMID: 27521895) J Med Chem. 2004 Mar 25;47(7):1750-9. (PMID: 15027866) J Med Chem. 2006 Oct 19;49(21):6177-96. (PMID: 17034125) Nature. 2001 Dec 13;414(6865):821-7. (PMID: 11742415) Curr Diabetes Rev. 2018;14(1):36-106. (PMID: 28474555) J Med Chem. 2020 Nov 12;63(21):12290-12358. (PMID: 32686940) J Cell Sci. 2009 Apr 1;122(Pt 7):893-903. (PMID: 19295123) Bioorg Chem. 2021 Oct;115:105151. (PMID: 34333424) |
| تواريخ الأحداث: | Date Created: 20210927 Latest Revision: 20210929 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8459440 |
| DOI: | 10.1021/acsomega.1c03600 |
| PMID: | 34568690 |
| قاعدة البيانات: | MEDLINE |
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