Synthesis, Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety

Kekeçmuhammed, Hüseyin; Tapera, Michael; Aydogdu, Ekrem; Sarıpınar, Emin; Karataş, Elanur Aydın; Üç, Eda Mehtap; Akyuz, Mesut; Tüzün, Burak; Gülçin, İlhami; Bora, Rıfat Emin

doi:10.1002/cbdv.202200886

Cited by 5 publications

(1 citation statement)

References 47 publications

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“…CADD has become increasingly important, especially in recent years, and has become a method that researchers use to understand how potential drugs interact with target molecules. In recent years, there have been several studies in the literature aimed at developing both anticancer drugs − and HCA inhibitors − using the CADD approach. On the other hand, drug-likeness and ADME analyses are also critical computational tools for drug discovery and development studies.…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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Peripheral (E)‐2‐[(4‐hydroxybenzylidene)‐3,4‐dihydronaphthalen‐1(2H)‐one)]‐coordinated phthalocyanines with improved enzyme inhibition properties and photophysicochemical behaviors

Güleç,

Bilgiçli,

Tüzün

et al. 2024

Archiv der Pharmazie

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In this study, (E)‐4‐{4‐[(1‐oxo‐3,4‐dihydronaphthalen‐2(1H)‐ylidene)methyl]phenoxy}phthalonitrile (4) and its phthalocyanine derivatives (5–8) were synthesized for the first time. Aggregation behaviors of the novel soluble phthalocyanines in organic solvents were investigated. In addition, the efficiency of 1O2 production of (5) and ZnPc (6) was investigated. The singlet oxygen quantum yields (ΦΔ) for 2HPc (5) and ZnPc (6) were found to be 0.58 and 0.83, respectively. Additionally, novel phthalocyanines (5–8) were investigated for their ability to inhibit enzymes. They exhibited a highly potent inhibition effect on human carbonic anhydrase I and II (hCA I and II) and α‐glycosidase (α‐Gly) enzymes. Ki values are in the range of 2.60 ± 9.87 to 11.53 ± 6.92 µM, 3.35 ± 0.53 to 15.47 ± 1.20 µM, and 28.60 ± 4.82 to 40.58 ± 7.37 nM, respectively. The calculations of the studied molecule at the B3LYP, HF, and M062X levels in the 6–31G basis sets were made using the Gaussian package program. Afterward, the interactions occurring in the docking calculation against a protein that is the crystal structure of hCA I (PDB ID: 2CAB), the crystal structure of hCA II (PDB ID: 5AML), and the crystal structure of α‐Gly (PDB ID: 1R47), were examined. Following that, Protein–Ligand Interaction Profiler (PLIP) analysis was used to look at the interactions that occurred during the docking calculation in further detail.

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Molecular hybrids integrated with imidazole and hydrazone structural motifs: Design, synthesis, biological evaluation, and molecular docking studies

Tapera,

Kekeçmuhammed,

Sarıpınar

et al. 2023

Journal of Molecular Liquids

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Synthesis, Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety

Cited by 5 publications

References 47 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

Peripheral (E)‐2‐[(4‐hydroxybenzylidene)‐3,4‐dihydronaphthalen‐1(2H)‐one)]‐coordinated phthalocyanines with improved enzyme inhibition properties and photophysicochemical behaviors

Molecular hybrids integrated with imidazole and hydrazone structural motifs: Design, synthesis, biological evaluation, and molecular docking studies

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