Computational Drug-Likeness Studies of Selected Thiosemicarbazones: A Sustainable Approach for Drug Designing

Drug intake, its absorption in the body, removal, and various side effects are factors considered when designing the drugs. Here, the in silico tools act as virtual shortcuts, assisting in the prediction of several important physicochemical properties like polar surface area (PSA), molecular weight, and molecular flexibility, etc., to evaluate probable drug leads as potential drug candidates. These tools also play a vital role in the prediction of the bioactivity score of probable drug leads against various human receptors. This paper presents a virtual combinatorial library of selected thiosemicarbazones (TSCs) and their metal complexes. Different properties like bioactivity score, physicochemical, distribution, absorption, excretion, metabolism, and toxicity (ADMET) parameters were assessed. By using ChemDraw Ultra 12.0, the structures of ligands and complexes were drawn and downloaded in PDB format. Physicochemical parameters were calculated using online softwares viz. Molinspiration and SwissADME, and ADMET properties were calculated using admetSAR (2.0). Molecular docking was performed using PyRx Python Prescription 0.8. with Janus Kinase and Transforming Growth Factor Beta (Tgf-β). Janus Kinase and Tgf-β are some cytokines involved in cell development, proliferation, and cell death. Three important TSCs, i.e., salicyldehyde thiosemicarbazone, acenaphthenequinone thiosemicarbazone, 2-chloronicotinic thiosemicarbazone, and their virtually designed complexes exhibited appreciable in silico results. Most ligands and complexes had good bioactivity values against all the biological targets.