Dataset Information

Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone.

ABSTRACT: To find novel human carbonic anhydrase (hCA) inhibitors, we synthesized thirteen compounds by combining thiazolidinone with benzenesulfonamide. The result of the X-ray single-crystal diffraction experiment confirmed the configuration of this class of compounds. The enzyme inhibition assays against hCA II and IX showed desirable potency profiles, as effective as the positive controls. The docking studies revealed that compounds (2) and (7) efficiently bound in the active site cavity of hCA IX by forming sufficient interactions with active site residues. The fragment of thiazolidinone played an important role in the binding of the molecules to the active site.

SUBMITTER: Zhang ZP

PROVIDER: S-EPMC6651801 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone.

Zhang Zuo-Peng ZP Yin Ze-Fa ZF Li Jia-Yue JY Wang Zhi-Peng ZP Wu Qian-Jie QJ Wang Jian J Liu Yang Y Cheng Mao-Sheng MS

Molecules (Basel, Switzerland) 20190630 13

To find novel human carbonic anhydrase (hCA) inhibitors, we synthesized thirteen compounds by combining thiazolidinone with benzenesulfonamide. The result of the X-ray single-crystal diffraction experiment confirmed the configuration of this class of compounds. The enzyme inhibition assays against hCA II and IX showed desirable potency profiles, as effective as the positive controls. The docking studies revealed that compounds (2) and (7) efficiently bound in the acti ...[more]

PMID: 31262068

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Project description:Changes in gene expression cause uncontrolled cell proliferation and consequently tumor hypoxia. The tumor cells shift their metabolism to anaerobic glycolysis with a significant modification in pH. Therefore, an over expression of carbonic anhydrase IX (CA IX) genes was detected in many solid tumors. Accordingly, selective inhibition of CA IX can be a useful target for discovering novel antiproliferative agents. The present study described the synthesis of new aryl thiazolone-benzenesulfonamides 4a-j as well as their carbonic anhydrase IX inhibitory effect. All the designed derivatives were evaluated for their anti-proliferative activity against triple-negative breast cancer cell line (as MDA-MB-231) and another breast cancer cell line (MCF-7) in addition to normal breast cell line MCF-10A. Compounds 4b-c, 4e, 4g-h showed significant inhibitory effect against both cancer cell lines at concentration ranges from 1.52-6.31 μM, with a high selectivity against breast cancer cell lines ranges from 5.5 to 17.5 times. Moreover, three sulfonamides derivatives 4e, 4g and 4h showed excellent enzyme inhibition against CA IX with IC50 10.93-25.06 nM and against CA II with IC50 1.55-3.92 μM that revealed their remarkable selectivity for CA IX over CA II. Additionally, 4e was able to induce apoptosis in MDA-MB-231 with a significant increase in the annexin V-FITC percent by 22 fold as compared with control. Cellular uptake on MDA-MB-231 cell lines were carried out using HPLC method on the three active compounds (4e, 4g and 4h). On the other hand inhibition of one or more CAs present in bacteria was reported to interfere with bacterial growth. So, the new benzenesulfonamides were evaluated against their antibacterial and anti-biofilm activities. Analogues 4e, 4g and 4h exhibited significant inhibition at 50 μg mL-1 concentration with 80.69%, 69.74% and 68.30% against S. aureus compared to the positive control CIP which was 99.2%, while compounds 4g and 4h showed potential anti-biofilm inhibition 79.46% and 77.52% against K. pneumonia. Furthermore, the designed compounds were docked into CA IX (human) protein (PDB ID: 5FL6) and molecular modeling studies revealed favorable binding interactions for the active inhibitors. Finally, the predictive ADMET studies showed that, compounds 4e, 4g and 4h possessed promising pharmacokinetic properties.

Dataset Information

Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone.

Publications

Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone.

Similar Datasets

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