Investigation of inhibitory effect of sulfated chitosan oligomer on human heparanase enzyme: in silico and in vitro studies

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dc.authoridAkkaya, Birnur AKKAYA/0000-0001-9139-1884
dc.authorwosidkocabay, samet/AAA-6158-2021
dc.contributor.authorKocabay, Samet
dc.contributor.authorAlagoez, M. Abdullah
dc.contributor.authorAkkaya, Birnur
dc.date.accessioned2024-08-04T20:55:07Z
dc.date.available2024-08-04T20:55:07Z
dc.date.issued2024
dc.departmentİnönü Üniversitesien_US
dc.description.abstractDeaths from cancer are widespread worldwide and the numbers continue to increase day by day. During the disease progression of cancer in cells, many of its metabolic activities change. Increased heparanase enzyme release is just one example. Following heparanase enzyme activity, many molecules interact with the remodeling of glycosaminoglycan structures, which triggers the release of different enzymes, cytokines, and growth factors, including fibroblast growth factors (FGF1 and FGF2), vascular endothelial growth factor (VEGF), hepatocyte growth factor, transforming growth factor beta and platelet-derived growth factor. These are the most important factors in metastasis due to the formation of new vascular structures caused by those elements. To reduce tumor growth and metastasis, various drugs have been designed by modifying chitosan and its derivatives. In this study, we used chitosan oligomer (A), sulfated chitosan oligomer (ShCsO) (B), heparin (C), phosphate monomer (D1) of PI-88 and sulfate monomer (D2) of PI-88 as heparanase inhibitors. We modified the chitosan oligomer with chlorosulfonic acid to synthesize ShCsO to investigate its inhibitory effects on human serum heparanase. Also examined were molecular docking; molecular dynamics (MD); adsorption, distribution, metabolism, elimination and toxicity (ADMET); and target prediction. ShCsO decreased enzyme activity at a concentration of 0.0001 mg/mL. The docking scores of A, B and C from in silico studies were -6.254, -6.936 and -6.980 kcal/mol, respectively, and the scores for the two different PI-88 monomers were -5.741 and -5.824 kcal/mol. These results show that ShCsO may be a potential drug candidate for treating cancer. Communicated by Ramaswamy H. Sarmaen_US
dc.description.sponsorshipTUBITAK (Trkiye Bilimsel ve Teknolojik Arascedil;timath;rma Kurumu; Scientific and Technological Research Council of Trkiye)en_US
dc.description.sponsorshipNo Statement Availableen_US
dc.identifier.doi10.1080/07391102.2024.2317421
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.pmid38410992en_US
dc.identifier.scopus2-s2.0-85186186981en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1080/07391102.2024.2317421
dc.identifier.urihttps://hdl.handle.net/11616/101845
dc.identifier.wosWOS:001175980300001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Incen_US
dc.relation.ispartofJournal of Biomolecular Structure & Dynamicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCanceren_US
dc.subjectangiogenesisen_US
dc.subjectmetastasisen_US
dc.subjectheparanaseen_US
dc.subjectchitosanen_US
dc.subjectsulfated chitosanen_US
dc.titleInvestigation of inhibitory effect of sulfated chitosan oligomer on human heparanase enzyme: in silico and in vitro studiesen_US
dc.typeArticleen_US

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