Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors

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creativework.keywordsBenzimidazole, Cytotoxicity, Dipeptidyl peptidase-4, Dual inhibition, Molecular dynamics, Xanthine oxidase
creativework.publisherElsevier Ireland Ltden
dc.contributor.authorTomovic K.
dc.contributor.authorIlic B.S.
dc.contributor.authorSmelcerovic Z.
dc.contributor.authorMiljkovic M.
dc.contributor.authorYancheva D.
dc.contributor.authorKojic M.
dc.contributor.authorMavrova A.T.
dc.contributor.authorKocic G.
dc.contributor.authorSmelcerovic A.
dc.date.accessioned2024-07-10T14:27:04Z
dc.date.accessioned2024-07-10T14:49:30Z
dc.date.available2024-07-10T14:27:04Z
dc.date.available2024-07-10T14:49:30Z
dc.date.issued2020-01-05
dc.description.abstractMultiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1–9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo[3,2-a]benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 μM, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 μM. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition.
dc.identifier.doi10.1016/j.cbi.2019.108873
dc.identifier.issn1872-7786
dc.identifier.issn0009-2797
dc.identifier.scopusSCOPUS_ID:85074070795en
dc.identifier.urihttps://rlib.uctm.edu/handle/123456789/553
dc.language.isoen
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074070795&origin=inward
dc.titleBenzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors
dc.typeArticle
oaire.citation.volume315
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