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.authoridTAHTACI, HAKAN/0000-0002-1557-6315
dc.authoridAkkoc, Senem/0000-0002-1260-9425
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.accessioned2024-09-29T15:50:38Z
dc.date.available2024-09-29T15:50:38Z
dc.date.issued2023
dc.departmentKarabük Üniversitesien_US
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.en_US
dc.description.sponsorshipResearch Fund of Karabuk University [KBUBAP-21-YL-072]; Research Fund of Suleyman Demirel University [TSG-2021-8458]en_US
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).en_US
dc.identifier.doi10.1002/cbdv.202200884
dc.identifier.issn1612-1872
dc.identifier.issn1612-1880
dc.identifier.issue1en_US
dc.identifier.pmid36445849en_US
dc.identifier.scopus2-s2.0-85143826409en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1002/cbdv.202200884
dc.identifier.urihttps://hdl.handle.net/20.500.14619/3649
dc.identifier.volume20en_US
dc.identifier.wosWOS:000898046500001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWiley-V C H Verlag Gmbhen_US
dc.relation.ispartofChemistry & Biodiversityen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectantiproliferative activityen_US
dc.subjectbioorganic chemistryen_US
dc.subjectcytotoxicityen_US
dc.subjectheterocyclesen_US
dc.subjectADMEen_US
dc.titleNovel Thioether-Bridged 2,6-Disubstituted and 2,5,6-Trisubstituted Imidazothiadiazole Analogues: Synthesis, Antiproliferative Activity, ADME, and Molecular Docking Studiesen_US
dc.typeArticleen_US

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