In silico Investigation on Isatin (1H-indole-2,3-dione) Derivatives as Potential AntiTumor Necrosis Factor-Alpha
http://www.doi.org/10.26538/tjnpr/v6i11.21
Keywords:
Inhibitory activity, Molecular docking, B3LYP, Binding Affinity, CancerAbstract
The role played by tumor necrosis factor-alpha (TNF-α) in advancing cancer has drawn the attention of many researchers. Thus, Isatin(1H-Indole-2,3-Dione) derivatives have been explored to curb this dreaded cancer-causing agent via semi-empirical (PM6) method. In order to obtain the descriptors that describe anti-tumor necrosis factor-alpha, the quantitative structure-activity relationship (QSAR) and molecular docking methods were used in this study. The ability of the studied compounds to acts as a drug were evaluated using Lipinski rule of five. The selected descriptors were used to develop QSAR model, which proved to be predictive, and this was confirmed and validated by considering the squared correlation coefficient (R2=0.89), adjusted squared correlation coefficient (adj. R2=0.89), cross validation (CV R2=0.87). The docked compounds 9, 14, and 16 against tumor necrosis factor-alpha (TNF-α) with -6.5 kcal/mol proved to be effective than other studied compounds as well as the referenced drug. Also, the correlation between the selected descriptors and calculated binding affinity was examined. It was observed that the plot of Log P against binding affinity obeyed 0.5≤x≤1, which showed that Log P contributed to inhibitory activities of the studied compounds against tumor necrosis
factor-alpha.
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