Abstract
Prostate cancer is the most prevalent deadly cancer in men worldwide. Androgen receptors are widely recognized for their prognostic and predictive roles in prostate cancer. The current study deals with the pharmacological analysis and preclinical trials of newly designed piperazine linked thiohydantoin derivatives incorporating various five or six-membered heterocyclic moieties using in silico techniques as androgen antagonist. The designed ligands were subjected to molecular properties prediction, solubility, toxicity and drug-likeness. ADMET profile was studied using admetSAR. All the ligands obeyed Lipinski’s rule and had good oral bioavailability. Enzlutamide was used as the standard drug. In silico docking, the analysis was carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. The compound was prioritised based on two important parameters like binding energy and inhibition constant. The results showed that all the ligands had binding energy ranging between − 11.1 and − 9.30 kcal/ mol and inhibition constant between 7.25 and 152.11 nM. Ligands L14, L12, L10 and L9 showed better binding affinity compared to the standard drug in docking simulation. The results indicate that the designed ligand, L14 is potential androgen antagonist and showing stability as well after interaction with receptor. The study could lead to the further development of potent androgen antagonist for the treatment of prostate cancer.
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Bhati, S., Kaushik, V. & Singh, J. In Silico Identification of Piperazine Linked Thiohydantoin Derivatives as Novel Androgen Antagonist in Prostate Cancer Treatment. Int J Pept Res Ther 25, 845–860 (2019). https://doi.org/10.1007/s10989-018-9734-5
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DOI: https://doi.org/10.1007/s10989-018-9734-5