Imidazole-Derived Alkyl and Aryl Ethers: Synthesis, Characterization, In Vitro Anticancer and Antioxidant Activities, Carbonic Anhydrase I-II Inhibition Properties, and In Silico Studies

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dc.authoridErdogan, Taner/0000-0001-7294-0331
dc.contributor.authorFaris, Mays
dc.contributor.authorBostanci, Hayrani Eren
dc.contributor.authorOzcan, Ibrahim
dc.contributor.authorOzturk, Mustafa
dc.contributor.authorKocyigit, Umit Muhammed
dc.contributor.authorErdogan, Taner
dc.contributor.authorTahtaci, Hakan
dc.date.accessioned2024-09-29T16:01:00Z
dc.date.available2024-09-29T16:01:00Z
dc.date.issued2024
dc.departmentKarabük Üniversitesien_US
dc.description.abstractImidazole derivatives display extensive applications in pharmaceutical chemistry and have been investigated as bioactive compounds for medicinal chemistry. In this study, besides the starting materials (3a-c and 4a-c), synthesis, characterization, and biological activity studies were conducted on a total of 18 compounds, nine of which are known and the other nine are original. The compounds investigated in the study are a series of alkyl (7-15) and aryl (16-24) ether derivatives bearing substituted phenyl and imidazole rings, which were characterized using various methods including H-1 NMR, C-13 NMR, FT-IR analysis, elemental analysis, and mass spectroscopy. Computer-aided drug design studies have been carried out to predict the biological activities of compounds. Besides DFT calculations, the binding affinities of the compounds to EGFR, VEGFR2, FGFR1, HSP90, hCA I, and hCA II were investigated. Additionally, drug-likeness and ADME analyses were performed on the compounds. Anticancer, antioxidant, and enzyme inhibition activity tests were performed in biological activity studies on the synthesized compounds. Among the synthesized compounds, compounds 17 and 19-24 generally exhibited inhibition profiles against the widespread cytosolic hCA I isozyme with IC50 values ranging from 4.13 to 15.67 nM and cytosolic hCA II isozyme with IC50 values ranging from 5.65 to 14.84 nM. L929 (mouse fibroblast cell line) was used as the control healthy cell line, and MCF7 (breast cancer), C6 (rat glioblastoma), and HT-29 (colon cancer) cells were used in cell culture studies as cancer cell lines. Before the study on cancer cells, all compounds were examined on healthy cells, and their cytotoxicity was determined. As a result of these data, studies continued with six compounds determined to be nontoxic. On cancerous cells, it was determined that compounds 3a, 3b, 4a, 4b, 4c, and 7 had cytotoxic effects on both colon cancer and brain tumors. It was found that compound 3b had a more toxic effect than cisplatin on the glioma cell line with an IC50 value of 10.721 +/- 0.38 mu M, and compound 3a had a more toxic effect on the colon cancer cell line with an IC50 value of 20.88 +/- 1.02 mu M. However, it was determined that the same compounds did not have a statistically significant effect on breast cancer. Flow cytometry studies also showed that when the IC50 dose of compound 3b was applied to the C6 cell line, the cells tended to early and late apoptosis. Additionally, it has been shown by flow cytometry that the cell cycle stops in the G0/G1 phase. A similar effect was observed in the colon cancer cell line with compound 3a. Compound 3b caused early and late apoptosis of the colon cancer cell line with the applied IC50 dose and stopped the cell cycle in the G0/G1 phase. Finally, the FRAP method studied all synthesized compounds' antioxidant effects. According to the measured antioxidant power results, it was determined that no compound had a more effective reducing power than vitamin E.en_US
dc.description.sponsorshipKarab?k ?niversitesi [KBUBAP-23-YL-019, FBA-2023-3427]; Research Fund of Karabuk Universityen_US
dc.description.sponsorshipThis work was supported by the Research Fund of Karabuk University (grant number KBUBAP-23-YL-019). The computational studies reported in this paper were performed at Kocaeli University (FBA-2023-3427).en_US
dc.identifier.doi10.1021/acsomega.4c00028
dc.identifier.endpage20956en_US
dc.identifier.issn2470-1343
dc.identifier.issue19en_US
dc.identifier.pmid38764643en_US
dc.identifier.scopus2-s2.0-85192244687en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage20937en_US
dc.identifier.urihttps://doi.org/10.1021/acsomega.4c00028
dc.identifier.urihttps://hdl.handle.net/20.500.14619/5482
dc.identifier.volume9en_US
dc.identifier.wosWOS:001225433400001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Chemical Socen_US
dc.relation.ispartofAcs Omegaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectDrug Discoveryen_US
dc.subjectAntimicrobial Activityen_US
dc.subjectScreening Librariesen_US
dc.subjectEstimate Solubilityen_US
dc.subjectMolecular Dockingen_US
dc.subjectDerivativesen_US
dc.subjectPredictionen_US
dc.subjectComplexesen_US
dc.subjectBioavailabilityen_US
dc.subjectCombinatorialen_US
dc.titleImidazole-Derived Alkyl and Aryl Ethers: Synthesis, Characterization, In Vitro Anticancer and Antioxidant Activities, Carbonic Anhydrase I-II Inhibition Properties, and In Silico Studiesen_US
dc.typeArticleen_US

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