Insightful Bio-Evaluation of 1,2,4-Thiadiazole-1,2,4-Triazole derivatives as Anti-ubiquitin Ligase Down-regulating Human Lung Cancer.

Abstract

Human lung cancer still remains one of the dangerous diseases among human being worldwide. The danger of this disease in medical world remains colossal and this has drawn the attention of seasoned researcher to find lasting solution to this menace. Thus, eight 1,2,4-thiadiazole-1,2,4-triazole derivatives were investigated to observe their anti-ubiquitin ligase thereby reducing human lung cancer. The software used to achieve this work were Spartan 14 (optimization), PANDEL (for generating 2D descriptors), Pymol (for treating downloaded protein), Autodock Tool (for locating binding site in the downloaded protein and for converting ligand and receptor to .pdbqt format from .pdb format), Auto dock vina (for docking calculation) and discovery studio (for viewing the non-bonding interaction between the docked complexes). Ten 2D descriptors were selected from the entire descriptors in order to describe anti-ubiquitin ligase properties of 1,2,4-thiadiazole-1,2,4-triazole derivatives. Also, the developed QSAR model was observed to be predictive using the closeness the experimental IC50 to the predicted IC50 as well as the correlation coefficient (0.990) and adjusted correlation coefficient (0.976). More so, the calculated binding showed that compound h (-6.9 kcal/mol) possess ability to inhibit ubiquitin ligase than other studied compounds as well as Etoposide (Standard). Keywords: 1,2,4-Thiadiazole, ubiquitin ligase, 1,2,4-Triazole, cancer, QSAR, Molecular docking