Novel Thioether-Bridged 2,6-Disubstituted and 2,5,6-Trisubstituted Imidazothiadiazole Analogues: Synthesis, Antiproliferative Activity, ADME, and Molecular Docking Studies

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dc.authoridAkkoc, Senem/0000-0002-1260-9425
dc.authoridTAHTACI, HAKAN/0000-0002-1557-6315
dc.contributor.authorOzcan, Ibrahim
dc.contributor.authorAkkoc, Senem
dc.contributor.authorAlici, Hakan
dc.contributor.authorCapanlar, Seval
dc.contributor.authorSahin, Onur
dc.contributor.authorTahtaci, Hakan
dc.date.accessioned2025-03-23T19:47:14Z
dc.date.available2025-03-23T19:47:14Z
dc.date.issued2023
dc.departmentSinop Üniversitesi
dc.description.abstractIn this study, starting from 2-amino-1,3,4-thiadiazole derivatives (3-5), a new series of 2,6-disubstituted (compounds 7-15) and 2,5,6-trisubstituted (compounds 16-33) imidazo[2,1-b][1,3,4]-thiadiazole derivatives were synthesized using cyclization and Mannich reaction mechanisms, respectively. All synthesized compounds were characterized by H-1-NMR, C-13-NMR, FT-IR, elemental analysis, and mass spectroscopy techniques. Also, X-ray diffraction analysis were used for compounds 4, 7, 11, 17, and 19. The cytotoxic effects of the new compounds on the viability of colon cancer cells (DLD-1), lung cancer cells (A549), and liver cancer cells (HepG2) were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in vitro. Compound 15 was found to be the most potent anticancer drug candidate in this series with an IC50 value of 3.63 mu M against HepG2 for 48 h. Moreover, the absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized compounds were calculated and thus, their potential to be safe drugs was evaluated. Finally, to support the biological activity experiments, molecular docking studies of these compounds were carried out on three different target cancer protein structures (PDB IDs: 5ETY, 1M17, and 3GCW), and the amino acids that play key roles in the binding of the compounds to these proteins were determined.
dc.description.sponsorshipResearch Fund of Karabuk University [KBUBAP-21-YL-072]; Research Fund of Suleyman Demirel University [TSG-2021-8458]
dc.description.sponsorshipThis work was supported by the Research Fund of Karabuk University (grant number KBUBAP-21-YL-072) and the Research Fund of Suleyman Demirel University (grant number TSG-2021-8458). The numerical calculations reported in this article were performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).
dc.identifier.doi10.1002/cbdv.202200884
dc.identifier.issn1612-1872
dc.identifier.issn1612-1880
dc.identifier.issue1
dc.identifier.pmid36445849
dc.identifier.scopus2-s2.0-85143826409
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1002/cbdv.202200884
dc.identifier.urihttps://hdl.handle.net/11486/7317
dc.identifier.volume20
dc.identifier.wosWOS:000898046500001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistry & Biodiversity
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250323
dc.subjectantiproliferative activity
dc.subjectbioorganic chemistry
dc.subjectcytotoxicity
dc.subjectheterocycles
dc.subjectADME
dc.titleNovel Thioether-Bridged 2,6-Disubstituted and 2,5,6-Trisubstituted Imidazothiadiazole Analogues: Synthesis, Antiproliferative Activity, ADME, and Molecular Docking Studies
dc.typeArticle

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