Molecular Docking and ADME-T Analysis of Cytotoxic Quinoline Derivatives: Potential Applications for the Treatment of Skin Cancer

Recent advances in computational drug discovery have significantly improved the search for effective treatments for skin cancer, where molecular docking and pharmacokinetics play an important role in identifying new drug-like compounds. This study explores the inhibitory potential of pyrrolopyrazole (4BKY), an enzyme linked to skin cancer progression, using 62 cytotoxic quinoline derivatives.Among these, Ligand 7 and Ligand 10 demonstrated the strongest binding affinities, with docking scores of -6.722 kcal/mol and -6.606 kcal/mol, respectively. Their enhanced stability and interaction with key residues GLU 87 and CYS 89 suggest promising inhibitory properties. In addition to docking analysis, these compounds underwent ADMET (Absorption, Distribution, Metabolism, and Excretion) analysis profiling using SWISSADME, pkCSM, to assess their pharmacokinetic Additionally, toxicity assessment was performed using the ProTox-II web server (https://tox-new.charite.de/protox_II/), predicting mutagenicity, carcinogenicity, immunotoxicity, and hepatic toxicity.. Findings indicate favorable drug-likeness, efficient synthesis, and compliance with Lipinski’s rule of five, supporting their viability as targeted skin cancer therapeutics. Based on these results, Ligand 7 and Ligand 10 emerge as strong candidates for further research and development in oncology. Future studies will focus on experimental validation and clinical trials to confirm their effectiveness and safety, potentially paving the way for innovative skin cancer treatment strategies involving quinoline-based compounds.