Design, Molecular Docking Studies and ADMET Prediction of Chalcones of Indole-Benzenesulfonyl Derivatives as Thioredoxin Inhibitor for Anticancer Activity.

CHALCONE; THIOREDOXIN; MOLECULAR docking; CHALCONES; ANTINEOPLASTIC agents; HYDROGEN bonding interactions

The indole nucleus offers a wide range of applications in medicinal chemistry, including anticancer activity. A series of novel indole chalcone derivatives containing benzyl-sulphonyl group were designed and in silico study was carried out against the thioredoxin system as an anticancer target. The drug-likeness properties of synthesized compounds were predicted. A study on the Passonline server predicts the compounds to have the least adverse reaction with thioredoxin inhibitor activity. As the designed compounds break not more than one 'rule of five', it can be concluded that these derivatives could be orally active. As per the ADMET analysis, except for C2 which contains para-substituted bromo, all the proposed compounds can be considered as safer lead molecules. According to the docking analysis, the derivatives showed a good binding affinity with the lowest minimum binding energy to the protein. According to the docking results, C3, C7, and C8 containing para chloro, para hydroxyl, and meta chloro groups, respectively, could be the powerful inhibitors among the derivatives. The molecules form hydrophobic and hydrogen bond interactions. C9 consisting of meta fluorine group may be a more potent thioredoxin inhibitor in comparison with Daucostero. Overall, the findings suggest that C3, C7, C8, and C9 compounds could be effective anticancer inhibitors of thioredoxin. The designed indole chalcones containing benzyl-sulfonyl group analogs could be safer and more or equivalent effective anticancer agents. Mini abstract: A series of novel indole chalcone derivatives containing benzylsulphonyl group were designed and screened for in silico thioredoxin inhibitory activity. The results indicate C3, C7, C8, and C9 compounds could have good drug-likeness, oral activity, and binding affinity to the crystal structure of human thioredoxin reductase enzyme out of the screened derivatives. Hence, could be considered for further study as anticancer inhibitors of thioredoxin. [ABSTRACT FROM AUTHOR]

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