In silico ADME prediction of designed pyrimidine derivatives for antiviral, antimalarial and anticancer potentials

Abstract

Pyrimidine-based compounds are known for their wide-ranging pharmacological activities. In this study, three novel pyrimidine derivatives-SV02, SM02, and SC02-designed through QSAR and GQSAR analyses, were evaluated in silico using the SwissADME tool to predict their pharmacokinetic profiles. These compounds, selectively chosen based on significant descriptors, were screened for ADME properties, including physicochemical parameters, lipophilicity, solubility, drug-likeness, and medicinal chemistry alerts. SV02, intended as an antiviral agent, displayed moderate lipophilicity (Consensus Log Po/w=2.23), low gastrointestinal absorption, and a high topological polar surface area (TPSA=181.70 Ų). SM02, designed for antimalarial activity, demonstrated high GI absorption, good oral bioavailability, and compliance with all major drug-likeness filters. SC02, an anticancer candidate, showed moderate solubility, acceptable lipophilicity, and reasonable drug-likeness parameters. The results suggest that SM02 possesses the most favorable ADME profile, whereas SV02 and SC02 may require optimization for better permeability and absorption. These findings underscore the importance of in silico screening to predict pharmacokinetic behavior early in the drug development pipeline.