Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

Ünver, Hakan; Çevik, Ulviye Acar; Bostancı, Hayrani Eren; Kaya, Özlem Aycan; Koçyiğit, Ümit M.

doi:10.1002/slct.202301641

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…Cell viabilities determined as a result of the maximum dose (100 μM) of the six compounds determined on cancer cells are shown in Figure . The IC 50 values of cisplatin found for the mentioned cell lines correlate with the results obtained in previously published articles. , …”

Section: Results and Discussionsupporting

confidence: 89%

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

Faris,

Bostancı,

Özcan

et al. 2024

ACS Omega

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Imidazole 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 1 H NMR, 13 C NMR, FT-IR analysis, elemental analysis, and mass spectroscopy. Computeraided 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, druglikeness 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 IC 50 values ranging from 4.13 to 15.67 nM and cytosolic hCA II isozyme with IC 50 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 IC 50 value of 10.721 ± 0.38 μM, and compound 3a had a more toxic effect on the colon cancer cell line with an IC 50 value of 20.88 ± 1.02 μM. 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 IC 50 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 IC 50 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.

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Section: Results and Discussionsupporting

confidence: 89%

“…The IC 50 values of cisplatin found for the mentioned cell lines correlate with the results obtained in previously published articles. 47 , 72 …”

Section: Results and Discussionmentioning

confidence: 99%

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

Faris,

Bostancı,

Özcan

et al. 2024

ACS Omega

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“…[3,4] Among the 12 hCA isoforms in the human body, hCA I and hCA II, in particular, play a role in epilepsy treatment as well as in other physiologically vital processes such as respiration, pH balance, electrolyte secretion, pathophysiology, and progression of vision loss in patients with diabetes and glaucoma patients. [5][6][7][8][9] Despite these innovations, drugs that inhibit hCA isoenzymes have many side effects. Owing to the multitude of known side effects, recent attention has been focused on the discovery of new alternative hCA inhibitors.…”

Section: Introductionmentioning

confidence: 99%

New Thiazole Derivatives: Carbonic Anhydrase I–II and Cholinesterase Inhibition Profiles, Molecular Docking Studies

Karakaya,

Ercetin,

Yıldırım

et al. 2024

ChemistrySelect

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Thiosemicarbazone derivative was obtained by the addition of thiosemicarbazide to 5‐nitro‐thiophene‐2‐carbaldehyde. The addition–cyclization of the 2‐bromoacetophenone derivative to thiosemicarbazone derivative gave the new thiazole derivatives (2 a‐k). Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), antioxidant, and human carbonic anhydrase (hCA) I and II isoform inhibitory activities of the thiazole derivatives 2 a‐k were investigated. The effects of thiazole derivatives on carbonic anhydrase I and II (hCA I–II) isoenzymes were examined in vitro using the esterase method. IC50 values for enzyme inhibition were found to be 2.661–22.712 μM for hCA I and 5.372–26.813 μM for hCA II. All derivatives reduced the activities of carbonic anhydrase I and II isoenzymes and were new potential inhibitor molecule candidates. These compounds were found to have minimal effects on AChE and BChE. The antioxidant properties of the target compounds were determined using DPPH and ferric ion‐chelating assays. In particular, compounds 2 k and 2 h had the highest antioxidant effect in the series with IC50 values of 30.11±0.008 μM and 30.21±0.006 μM, respectively. ADMET properties of the compounds found to be effective were evaluated and their interactions with the enzyme were determined by molecular docking.

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Synthesis of novel 1,2,3-triazole-tethered N-acyl hydrazones as a new class of carbonic anhydrase II inhibitors: In vitro and in silico potentials

Fatima,

Saeed,

Ullah

et al. 2024

Bioorganic Chemistry

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Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

Cited by 4 publications

References 38 publications

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

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

New Thiazole Derivatives: Carbonic Anhydrase I–II and Cholinesterase Inhibition Profiles, Molecular Docking Studies

Synthesis of novel 1,2,3-triazole-tethered N-acyl hydrazones as a new class of carbonic anhydrase II inhibitors: In vitro and in silico potentials

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