Computational Descriptor Profiling and QSAR-Based Toxicity Assessment of a Nitro-Amino Substituted Uracil Derivative

Abstract

6-Amino-5-nitro-1,3-dimethyluracil (ANDMU) is a nitrogen- and oxygen-rich heterocyclic compound structurally analogous to uracil derivatives. Although such substituted pyrimidinone frameworks exhibit diverse physicochemical and biological behaviors, their computational characterization remains limited. In this study, a comprehensive descriptor-based profiling of ANDMU was performed to elucidate its constitutional, topological, electro-topological, and physicochemical features. The molecule exhibits a heteroatom-dense architecture with a high Sanderson electronegativity (Se= 23.48; PaDEL-normalized carbon-scaled value) and pronounced electrotopological variation (Ss=48.67), reflecting strong intramolecular electronic polarization. Toxicity estimates obtained using the U.S. EPA Toxicity Estimation Software Tool (T.E.S.T.) indicate a fathead minnow LC50 value consistent with moderate aquatic toxicity and a bioconcentration factor (log10 BCF) indicative of low bioaccumulation. Additional physicochemical predictions such as density (1.30 g/cm³) and vapor pressure (log10 mmHg = -0.85) support a low-volatility profile. StopTox consensus classifiers suggest moderate acute oral toxicity, a high likelihood of eye irritation (80% confidence), and low inhalation and dermal toxicity. Applicability domain assessments confirm that most predictions lie within reliable chemical space. This study provides the first integrated computational evaluation of ANDMU, offering quantitative insights into its structural organization and potential toxicological behavior.