Identification of some novel amide conjugates as potent and gastric sparing anti-inflammatory agents: In vitro, in vivo, in silico studies and drug safety evaluation

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dc.authoridkucukguzel, ilkay/0000-0002-7188-1859
dc.authoridHelvacioglu Akyuz, Sinem/0000-0002-3144-5024
dc.authoridcharehsaz, mohammad/0000-0002-4545-0756
dc.authoridGURSOY, SULE/0000-0001-5236-5974
dc.authorwosidGürsoy, Şule/JPW-8593-2023
dc.authorwosidkucukguzel, ilkay/Z-1541-2019
dc.authorwosidHelvacioglu Akyuz, Sinem/GWQ-9714-2022
dc.contributor.authorKulabas, Necla
dc.contributor.authorSet, Irem
dc.contributor.authorAktay, Goeknur
dc.contributor.authorGursoy, Sule
dc.contributor.authorDanis, Oezkan
dc.contributor.authorOgan, Ayse
dc.contributor.authorErdem, Safiye Sag
dc.date.accessioned2024-08-04T20:53:36Z
dc.date.available2024-08-04T20:53:36Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractToday, usage of NSAIDs (nonsteroidal anti-inflammatory drugs) is very common. However, it has been proven by many studies that NSAIDs with free carboxylic acid group damage the GI (gastrointestinal) system. Our aim was to mask the acidic groups of NSAIDs to prevent or reduce their side effects while preserving their pharmacological effects. In this study, new amide derivatives of known NSAIDs, compounds 11 -20 , were synthesized to investigate their analgesic and anti-inflammatory effects using in vivo models. While compound 11 showed the most remarkable anti-inflammatory activity by 60.9% inhibition value at 200 mg/kg dose, compounds 11, 12, 15 and 18 had almost the same analgesic activity to that of acetylsalicylic acid (100 mg/kg) and flurbiprofen (100 mg/kg). In addition, all test compounds used at high dose (200 mg/kg, p.o) did not show any acute toxicity. COX-1 and COX-2 inhibition properties of all compounds were measured by biochemical methods and the interaction of the most active compounds with COX enzymes is elucidated by computer-assisted virtual screening methods. It was determined by in vitro enzyme inhibition studies that compound 11 and 13 , synthesized from selective COX-1 inhibitors dexketoprofen and flurbiprofen, are selective COX-2 inhibitors. Moreover, compounds 11 -13 were found to be non-mutagenic according to the mutagenicity assay using Salmonella TA98 and TA10 0 strains with and without metabolic activation. Finally, the prediction of ADMET profile and drug-likeness properties of compounds 11 -20 were examined and the obtained results were evaluated. & COPY; 2023 Elsevier B.V. All rights reserved.en_US
dc.description.sponsorshipMarmara University, Scientific Research Projects Committee [SAG-B-080715-0314]en_US
dc.description.sponsorshipThis research was supported by Marmara University , Scientific Research Projects Committee; Project Number: SAG-B-080715-0314. The authors are grateful to Dr. Juergen Gross from the Institute of Organic Chemistry, University of Heidelberg , for his generous help on obtaining high resolution mass spectra of the compounds. Some of the drug substances used in this study were donated as gifts by Abdi Ibrahim, Atabay, DEVA and Sanovel Pharmaceutical Companies.en_US
dc.identifier.doi10.1016/j.molstruc.2023.135521
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.scopus2-s2.0-85152143267en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2023.135521
dc.identifier.urihttps://hdl.handle.net/11616/101284
dc.identifier.volume1285en_US
dc.identifier.wosWOS:001054350500001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal of Molecular Structureen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAnalgesic effecten_US
dc.subjectAnti-inflammatory effecten_US
dc.subjectMolecular modelingen_US
dc.subjectNon -steroid anti-inflammatory drugsen_US
dc.subjectCyclooxygenase (COX) inhibitorsen_US
dc.titleIdentification of some novel amide conjugates as potent and gastric sparing anti-inflammatory agents: In vitro, in vivo, in silico studies and drug safety evaluationen_US
dc.typeArticleen_US

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