Identification of N-(4-acetyl-4,5-dihydro-5-(7,8,9-substituted-tetrazolo[1,5-a]-quinolin-4-yl)-1,3,4-thiadiazol-2-yl) acetamide derivatives as potential caspase-3 inhibitors via detailed computational investigations

The current study included density function theory calculations, molecular docking studies, SeeSAR analysis, molecular dynamics studies and assessments of the absorption, distribution, metabolism, excretion and toxicity properties (ADMET) of N-(4-acetyl-4,5-dihydro-5-(7,8,9-substituted-tetrazolo[1,5-a] acetamides of -quinolin-4-yl)-1,3,4-thiadiazol-2-yl) that is 4a-j. These derivatives have previously been identified as anticancer agents against a human cervical cancer cell line. The primary goal of this work is to assess the potential of these derivatives as caspase-3 inhibitors using extensive computational analysis. The binding interactions of these compounds with caspase-3 protein (PDB ID: 4JJ8) were found and all compounds demonstrated strong binding interactions within the active pocket of the targeted protein. Interestingly, derivative 4e showed maximum potential and was found to have the strongest interactions with a binding energy of −29.6 kJ/mol. Furthermore, the findings were discovered to be in comparison with the reference drug, adriamycin (−26.5 kJ/mol). In addition to molecular docking, ADMET and simulation studies were carried out to determine their safety profiles, with the results correlating to molecular docking investigations. Finally, SeeSAR analysis and molecular dynamics simulation investigations were carried out. In conclusion, this molecule may be a “lead candidate’ for making a more powerful caspase-3 inhibitor that can be used in tumors where the levels of caspase-3 are aberrantly high.