Computational screening of Thiohydantoin Derivatives for antitumor activity

Abstract

A tumor may be defined as a mass of cells formed by accumulation of abnormal cells. Under normal conditions, as the cells in our body undergo senescence, they are replaced by new cells. This normal cell cycle is disrupted in cancer. Unlike normal cells which die after becoming old, tumor cells keep on multiplying regardless of the requirement of the body. As cells continue to get added to the mass, the tumor keeps on proliferating. The genes ErbB3 and erbB2 as heterodimerization partners are involved in various important pathways like growth and proliferation of cancer cells, resistance to chemotherapy as well as boosting metastasis. They are associated with therapeutic resistance having specific targets in various types of cancers including resistance to breast, head, neck, prostate cancers and many more. The study presented in this paper manages the pharmacological investigation and preclinical trials of a designed Receptor; tyrosine-protein kinase erbB-3 interacted to thiohydantoin subordinates fusing different five or six-membered heterocyclic moieties, which can be used as a potential antagonist as shown by in-silico techniques. The ligands thus designed were then analysed using various techniques, such as molecular property prediction, toxicity, solubility and drug-likeness. Its ADMET profile was studied by means of admetSAR. It was observed that all the potential ligands under study had a satisfactory oral bioavailability. They also obeyed Lipinski’s rule. PatchDock was used for analysing the in-silico docking. Priority was given on two salient parameters; Atomic contact energy & Score. Results indicate that all the ligands were having atomic contact energy ranging between – 223.89 and – 327.98 kcal / mol and score between 4690 and 5184. Ligands L07, L13, L03 and L15 have shown improved binding affinity as compared to the benchmark drug. Results stipulate that the designed ligand L03 is a potential antagonist which is exhibiting a stable interaction with the receptor.