Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells

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dc.contributor.authorZoatier, Bayan
dc.contributor.authorYildiztekin, K. Gizem
dc.contributor.authorAlagoz, M. Abdullah
dc.contributor.authorHepokur, Ceylan
dc.contributor.authorBurmaoglu, Serdar
dc.contributor.authorAlgul, Oztekin
dc.date.accessioned2025-05-04T16:47:37Z
dc.date.available2025-05-04T16:47:37Z
dc.date.issued2025
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractType V MAPK inhibitors are distinguished by their capacity to target both the ATP binding site and a specific allosteric site on the enzyme. The present work utilized in silico analysis with Maestro 13.8.135 (Schrodinger) software in conjunction with experimental investigations to enhance the antiproliferative efficacy and forecast the likely mechanism of action of benzothiazole derivatives. Approximately 28 compounds were developed, produced, and assessed for their antiproliferative properties against two breast cancer cell lines: ER+ (MCF7) and ER- (MDA-MB-231), in addition to one normal mouse fibroblast cell line (L929). Their antiproliferative activities were evaluated via the MTT test, with doxorubicin and cisplatin serving as reference drugs for comparison. Consequently, the compounds with the greatest activity against the MCF7 cell line were chosen, and their inhibitory effects on the p38 alpha MAPK enzyme were examined. The molecular docking studies of compounds 15 and 19 demonstrated significant binding affinities for p38 alpha MAPK. Molecular dynamics simulations conducted over 100 ns revealed that compounds 15 and 19 exhibit stability inside both the ATP-binding domain and the lipid domain of p38 alpha MAPK. The research focused on creating effective Type V MAPK inhibitors demonstrate that compounds 15 and 19 possess considerable ability to inhibit p38 alpha MAPK, hence establishing them as promising anticancer agents.
dc.description.sponsorshipBAP Projects of Mersin University [2020-1-TP3-4028]
dc.description.sponsorshipThis study was supported by 2020-1-TP3-4028 BAP Projects of Mersin University.
dc.identifier.doi10.1002/ardp.202500011
dc.identifier.issn0365-6233
dc.identifier.issn1521-4184
dc.identifier.issue4
dc.identifier.pmid40194955
dc.identifier.scopus2-s2.0-105002113158
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1002/ardp.202500011
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35674
dc.identifier.volume358
dc.identifier.wosWOS:001460701900001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofArchiv Der Pharmazie
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250504
dc.subjectantiproliferative effect
dc.subjectbenzothiazole
dc.subjectMCF7
dc.subjectmolecular docking
dc.subjectMTT assay
dc.subjectp38 alpha MAPK
dc.titleDevelopment of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells
dc.typeArticle

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