A QSAR and similarity search based on 1,2-benzisothiazol-3-ones to identify potential new inhibitors of caspase-3.

Among the neurodegenerative diseases responsible for cases of dementia, Alzheimer's disease (AD) is responsible for 60–80% of cases. Caspase-3 is an enzyme essential in the synaptic degeneration caused by this disease, as it acts on the cleavage of tau and APP proteins, which leads to the formation of β-amyloid plaques in the brain. Therefore, the inhibition of caspase-3 may be an effective treatment method. In this work, QSAR studies based on descriptors derived from SMILES, similarity search, toxicity, and ADME studies were performed, including an evaluation of the applicability domain based on 71 1,2-benzisothiazol-3-ones capable of inhibiting caspase-3. Among the three hits identified, H2 proved to be the most interesting hit to be explored. Therefore, this hit was selected for future biological assay studies to confirm its activity. It may indicate new and original caspase inhibitors with drug-like properties suitable for AD therapy. [ABSTRACT FROM AUTHOR]