In Silico Molecular Modeling and Prediction of ADMET Properties for Novel Dioxoisoindoline Derivatives as Anticancer Agents
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Abstract
The decreased efficiency of the existing anticancer drugs is an unsolved problem in both basic and advanced medicine. Conducting theoretical chemical studies to identify possible drug candidates using Dioxoisoindoline derivatives is one of the proposed solutions to this problem. This specific study applied molecular docking and ΔG calculations to evaluate the activity of dioxoisoindoline derivatives against cancer-related proteins. The higher the negative ΔG value, the better the match between the compound and protein interactions. According to this study, five compounds (R1_R5) presented significant activity against various proteins. All of them presented high negative values—especially the two compounds R3 and R4, which showed high effectiveness against six cancer-related proteins. The achieved ΔG values for all derivatives were within a suitable range, suggesting their capability as therapeutic agents. According to these results, the Dioxoisoindoline derivatives under observation show the potential to target different cancer-related proteins. A Density Functional Theory study was performed to determine the Lowest Unoccupied Molecular Orbital and Highest Occupied Molecular Orbital for five compounds. It was used to calculate the gap, Electron affinity, Ionization Potential, Electronegativity, Softness and Hardness of the molecules. The online in silico prediction model ADMET lab 3.0 was used to determine ADMET attributes such as Molecular weight, Number of hydrogen bond donors, Number of hydrogen bond acceptors, the logarithm of the n-octanol/water distribution coefficient, topological polar surface area and Boiling point. The physicochemical properties of all five compounds were determined, and they were found to meet the Lipinski rule of five (i.e., the drug-like rule). Overall, the study highlights the importance of developing alternative anticancer medications and recommends further research and development of potential anticancer drugs.
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