In silico activities, toxicity profiles and dug-like properties of some pyridazinyl benzenesulfonamides as a COX-inhibitor and antineoplastic agent

This study was designed to predict in silico cyclooxygenase-2 (COX-2) inhibitory, antineoplastic activities, and toxicity profile of some benzenesulfonamide-pyridazinone derivatives, since COX-2 inhibitors have significant antineoplastic activity and cardiotoxicity. The result suggested that the biological activity score has revealed that compounds 12, 13, and 21 have the highest protease enzyme inhibitory activity compare to standard drug celecoxib. All the compounds follow Lipinski’s rule of 5 except celecoxib and compound 21. Predicted ligand-target interaction has showed that celecoxib and compound 6 have COX-2 inhibitory activity. Compounds 2-7, 10, and 19 targets the cell division control protein homologies with their specific E values. The remaining compounds are carbonic anhydrase inhibitors. Compound 18 did not show any specific targets. Celecoxib, compound 7, and 14, can act on breast ductal cell carcinoma with probability value (Pa) values0.640, 0.626, and 0.625, respectively. Compound 17 act on glioblastoma with Pa value of 0.667. The remaining compound act on non-small cell carcinoma with compound 7 has a high Pa value of 0.760. All the compounds have the probability of hERG blocking activity except compound 18. Compounds 1, 19, and 21 have the highest blocking probability. All the compounds are showing hepatotoxicity among them compounds 3, 4, 9, 10, 11, 13, 14, 15, and 16 have the highest toxicity probability. All the compounds are Ames negative. As carbonic anhydrase enzyme is now a promising therapeutic target for cancer, the present compounds understudy may show promising activity as a COX inhibitor as well as anticancer compounds. “CLC pred” results also strengthening our prediction that maximum compounds are better acting on non-small cell lung carcinoma (NSCLC).