Design and synthesis of thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen as potential MetAP (type II) inhibitors

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dc.authorid0000-0003-3892-2775
dc.authorid0000-0003-3295-7344
dc.authorid0000-0003-2647-2033
dc.authorid0000-0002-9325-3757
dc.authorid0000-0003-0855-4617
dc.authorid0000-0001-7051-3125
dc.authorid0000-0002-8858-4500
dc.authorid0009-0003-9152-5143
dc.authorid0000-0002-2576-3085
dc.authorid0000-0002-0052-4926
dc.authorid0000-0001-9405-8905
dc.contributor.authorYılmaz, Özgür
dc.contributor.authorBiliz, Yağmur
dc.contributor.authorAyan, Sümeyra
dc.contributor.authorÇevik, Özge
dc.contributor.authorKarahasanoğlu, Müfide
dc.contributor.authorÇotuker, Reyhan
dc.contributor.authorMert Şahin, Naz Mina
dc.contributor.authorGökkaya, Kübra
dc.contributor.authorGülyüz, Sevgi
dc.contributor.authorYelekçi, Kemal
dc.contributor.authorKüçükgüzel, Ş. Güniz
dc.date.accessioned2025-05-14T15:15:57Z
dc.date.available2025-05-14T15:15:57Z
dc.date.issued2025
dc.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Kimya Mühendisliği Bölümü
dc.description.abstractIn the present study, a range of novel thiosemicarbazides 4a-i and 1,2,4-triazoles 5a-i derived from ibuprofen, were synthesized. Structural elucidation of these synthesized compounds was performed utilizing a variety of spectroscopic methods, including FTIR, 1 H NMR, 13C NMR and HR-MS. The synthesized compounds were tested for cytotoxicity in five different cancer cell lines (cervical cancer (HeLa), human breast cancer (MCF-7), human gastric adenocarcinoma (MKN-45), human metastatic prostate cancer (PC3) and human glioblastoma (U87)). The compounds were compared with healthy cells (NIH-3T3) and the most effective compounds were determined by means of the selectivity index. Thiosemicarbazides derived form ibuprofen 4i and 4d showed anticancer activity, while 1,2,4-triazoles derived form ibuprofen 5b, 5c, 5d, 5e, 5h, 5g showed anticancer activity in HeLa, MCF-7, MKN-45, PC3 and U87 cells. To test the stability of the protein-drug complexes all 18 compounds 4a-i and 5a-i were docked into the active site of the MetAP2 enzyme In general, computational inhibition constants values were correlated with the experimental values. The dynamic behavior of MetAP2-inhibitor complexes was analyzed using all atoms Molecular Dynamic (MD) simulations for 200 ns duration. MD revealed that the drugs bind in the active center of MetAP2 with stable RMSD and RMSF. In conclusion, in-silico results and in-vitro studies suggests that thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen may be novel anticancer drug candidates for treating cervical, breast, prostate, gastric and glioblastoma. Compounds provided induction of apoptotic proteins in the cell by inhibiting MetAP2 enzyme. Furthermore, the potential antioxidant activities of the compounds were evaluated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay. Among the compounds tested, 4a, 4b, 4e, 4f, 4h, and 4i exhibited values closely resembling the DPPH activity of the standards.
dc.description.sponsorshipThis study was funded by the Turkish Health Institutes Presidency (TUSEB). Project number: 4235. Bu çalışma, Türkiye Sağlık Enstitüleri Başkanlığı (TUSEB) tarafından finanse edilmiştir. Proje numarası: 4235.
dc.identifier.citationYılmaz, Ö., Biliz, Y., Ayan, S., Çevik, Ö., Karahasanoğlu, M., Çotuker, R., Mert Şahin, N. M., Gökkaya, K., Gülyüz, S., Yelekçi, K., & Küçükgüzel, Ş. G. (2025). Design and synthesis of thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen as potential MetAP (type II) inhibitors. Chemico-Biological Interactions, 416, pp. 1-14. https://doi.org/10.1016/j.cbi.2025.111555
dc.identifier.doi10.1016/j.cbi.2025.111555
dc.identifier.endpage14
dc.identifier.issn0009-2797
dc.identifier.pmid40345475
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1016/j.cbi.2025.111555
dc.identifier.urihttps://hdl.handle.net/20.500.13055/983
dc.identifier.volume416
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorBiliz, Yağmur
dc.institutionauthorid0000-0003-3295-7344
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofChemico-Biological Interactions
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectThiosemicarbazide
dc.subject1
dc.subject2
dc.subject4-triazole
dc.subjectIbuprofen
dc.subjectCytotoxicity
dc.subjectMetAP2
dc.subjectAntioxidant
dc.subjectMolecular Modeling
dc.titleDesign and synthesis of thiosemicarbazides and 1,2,4-triazoles derived from ibuprofen as potential MetAP (type II) inhibitors
dc.typeArticle
dspace.entity.typePublication

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