Physicochemical, biological, and toxicological studies of pyridine and its derivatives: an in-silico approach

Pyridine and its derivatives are extensively used as solvents and precursors in the pharmaceutical and chemical industries. However, their persistent nature, high water solubility, and potential for environmental contamination raise concerns about their impact on human health and ecosystems. This study employs an in-silico approach to evaluate the physicochemical, spectral, biological, and pharmacokinetic properties of pyridine and selected derivatives. Using density functional theory (DFT) with the B3LYP/6- 311 g + + (d,p) basis set, we analyze their reactivity and spectral behaviors. Among the analyzed derivatives of 2-fluoropyridine, 6-fluoropyridine- 3-amine exhibits the lowest HOMO–LUMO gap, indicating higher reactivity, while bromine-substituted 2-fluoropyridine shows the highest free energy values. Molecular docking studies and nonbonding interaction calculations reveal that pyridine exhibits the lowest binding affinity to human kinesin Eg5, while 6-fluoronicotinic acid demonstrates the strongest affinity. Furthermore, 100 ns molecular dynamics simulations assess the protein–ligand interactions and the deformability of amino acid residues. Biological and toxicological evaluations through ADMET and PASS predictions show that while all compounds are non-carcinogenic, they may induce adverse effects such as red cell aplasia, multiple organ failure, sideroblastic anemia, aphthous ulcers, hematemesis, and nail discoloration. The findings from this research can enhance public awareness and offer valuable insights into the biochemical and toxicological impacts of these substances on human health and the environment.