Potential inhibitors of human carbonic anhydrase isozymes I and II: Design, synthesis and docking studies of new 1,3,4-thiadiazole derivatives

Altıntop, Mehlika Dilek; Sever, Belgin; Özdemir, Ahmet; Küçükoğlu, Kaan; Önem, Hicran; Nadaroğlu, Hayrünnisa; Kaplancıklı, Zafer Asım

doi:10.1016/j.bmc.2017.05.005

Cited by 21 publications

(14 citation statements)

References 35 publications

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“…Cyclohexyl isothiocyanate (0.1 mol, 15 mL) and hydrazine hydrate (0.2 mol) were stirred in ethanol (150 mL) at room temperature. After the completion of the reaction, the precipitated product ( 1 ) was filtered and recrystallized from ethanol [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…Compound 1 (0.09 mol) was dissolved in ethanol (150 mL) and a solution of NaOH (0.1 mol) in ethanol was added. Carbon disulfide (0.1 mol, 6 mL) was added and the mixture was refluxed for 8 h. After this period, the solution was cooled and acidified to pH4–5 with hydrochloric acid solution and crystallized from ethanol [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…A mixture of compound 2 (0.08 mol), ethyl bromopropionate (0.08 mol) and potassium carbonate (0.09 mol) was stirred under reflux for 9 h in acetone (150 mL). The solvent was evaporated under reduced pressure and the product was washed with water, dried and crystallized from ethanol [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

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Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity

et al. 2017

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In the field of infection management, it is a major challenge to discover a potent and safe antifungal agent due to the emergence of resistant strains. Hence, the goal of this paper is to design and synthesize novel oxadiazole-thiadiazole hybrid compounds (6a–6s) and evaluate their antifungal activity. The structures of synthesized compounds were elucidated by various methods including FT-IR, 1H-NMR, 13C-NMR and HR-MS spectral data. Compounds were tested against four Candida species by broth microdilution assay. Compounds 6e, 6k and 6r, bearing a nitro group, showed significant antifungal activity against all fungi with minimum inhibitory concentration (MIC) in the range of 0.78–3.12 µg/mL. These compounds were also screened for their in vitro cytotoxic effects by MTT assay and detected as nontoxic at their active concentrations against Candida strains. To examine the effects of these compounds on ergosterol biosynthesis, the LC-MS-MS method, which is based on quantification of ergosterol level in C. krusei, was carried out. Finally, the most active molecule (6e) was docked in the active site of the lanosterol 14α-demethylase enzyme, and it was determined that there is a strong interaction between the compound and enzyme.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity

et al. 2017

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“…Hydrazine monohydrate (5 mmol) was added dropwise to a solution of 1 mmol urea compound in ethanol on a magnetic stirrer. The mixture was stirred at room temperature over a period of 8 h. The residue was filtered, washed with water, and dried [22].…”

Section: General Procedures Of Hydrazide Synthesismentioning

confidence: 99%

Design, synthesis, biological evaluation and molecular docking of novel moleculesto PARP-1 enzyme

Tok¹,

Kaymakçıoğlu²,

İlhan³

et al. 2019

Turk J Chem

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Poly (ADP-ribose) polymerase (PARP) enzyme catalyzes the transfer of ADP-ribose into target proteins.Therefore, PARP is responsible for DNA repair, cell proliferation, and cell death. In this study, potential PARP enzyme inhibitors were designed and synthesized. The synthesized compounds were elucidated by Fourier-transform infrared spectroscopy, 1 H NMR, 13 C NMR, heteronuclear single-quantum correlation, and mass spectrometry, and their purity was checked via thin-layer chromatography, high-performance liquid chromatography, and elemental analysis. A total of 63 newly synthesized compounds were screened in terms of PARP inhibition by cellular PARylation assay in the HeLa cell line. It was found that 19 compounds significantly inhibited the H 2 O 2 -induced cellular PARylation. The chemosensitizer effect of these compounds in cancer cells treated with doxorubicin (doxo) was investigated. It was found that the combination of potent PARP inhibitors with doxo potentiated a cytotoxic effect, similar to that of olaparib. The results of the molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed that compound 60 might be classified as a potential PARP inhibitor candidate. Taken together, all of the results suggested that carbohydrazide derivatives could be a promising lead for the treatment for cancer disorders.

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“…Carbonic anhydrase contains Zn +2 ion as Lewis acid which assists in binding of the active substrate with the water molecule. Zn +2 is tightly bound with three histidine units . The nucleophilic oxygen of water molecule attacks the electrophilic carbon of carbon dioxide to form the complex with zinc ions which then collapse to release bicarbonate ions (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Extending the scope of amantadine drug by incorporation of phenolic azo Schiff bases as potent selective inhibitors of carbonic anhydrase II, drug‐likeness and binding analysis

et al. 2018

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A series of Amantadine-based azo Schiff base dyes 6a-6e have been synthesized and characterized by H NMR and C NMR and evaluated for their in vitro carbonic anhydrase II inhibition activity and antioxidant activity. All of the synthesized showed excellent carbonic inhibition. Compound 6b was found to be the most potent derivative in the series, and the IC of 6b was found to be 0.0849 ± 0.00245 μm (standard Acetazolamide IC = 0.9975 ± 0.049 μm). The binding interactions of the most active analogs were confirmed through molecular docking studies. Docking studies showed 6b is interacting by making two hydrogen bonds w at His93 and Ser1 residues, respectively. All compounds showed a good drug score and followed Lipinski's rule. In summary, our studies have shown that these amantadine-derived phenolic azo Schiff base derivatives are a new class of carbonic anhydrase II inhibitors.

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Potential inhibitors of human carbonic anhydrase isozymes I and II: Design, synthesis and docking studies of new 1,3,4-thiadiazole derivatives

Cited by 21 publications

References 35 publications

Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity

Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity

Design, synthesis, biological evaluation and molecular docking of novel moleculesto PARP-1 enzyme

Extending the scope of amantadine drug by incorporation of phenolic azo Schiff bases as potent selective inhibitors of carbonic anhydrase II, drug‐likeness and binding analysis

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