Abstract
Neurodegenerative disorders are consequences of progressive and irreversible loss of neurons due to unwanted apoptosis, which involves caspases, a group of cystein proteases that cleave other proteins and inactivate them. Among several different groups of caspase enzymes, caspases-3 play a key role in apoptosis. Therefore they are used as therapeutic target for their inhibitors. In pursuit of better caspase-3 inhibitors, a quantitative structure–activity relationship analysis was performed on a series of 1,3-dioxo-4-methyl-2, 3-dihydro-1H-pyrrolo [3,4-c] quinolines as caspase-3 inhibitors using WIN CAChe 6.1 and Medicinal Chemistry Regression Machine. The best QSAR model was selected and validated. The values of the statistical data are r = 0.951, F = 65.62, SEE = 0.4175, t = 2.08. The study reveals that, if the partition coefficient (log P), conformational minimum energy (CME), and the lowest unoccupied molecular orbital energy (E LUMO) are altered, the biological activity is increased. On the basis of the selected QSAR model, we designed a new series of compounds, calculated their activity, and found that the compounds were more potent than existing compounds.
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One of the authors Mr. Simant Sharma is grateful to U.G.C. for providing a fellowship for this work.
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Sharma, S., Sahu, K., Jain, P. et al. QSAR study of 1,3–dioxo-4-methyl-2,3-dihydro-1h-pyrrolo[3,4-c]quinolines as caspase-3 inhibitors. Med Chem Res 17, 399–411 (2008). https://doi.org/10.1007/s00044-007-9075-y
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DOI: https://doi.org/10.1007/s00044-007-9075-y