DFT analysis and in silico exploration of drug-likeness, toxicity prediction, bioactivity score, and chemical reactivity properties of the urolithins

Abstract

Urolithins (Uro) are human microflora-derived metabolites of ellagic acid and ellagitannins. It has been shown to be a powerful modulator of oxidative stress, agents with potential anti-inflammatory, antiproliferative, and antiaging properties. The present study aimed to explore the drug-likeness, toxicity, and bioactivity score of urolithins that were required to be considered oral drug-active using the web-based softwares, Molinspiration, and protox_II. In addition, the chemical reactivity descriptors of the urolithins (Uro A, Uro B, Uro, C, Uro D) were also determined through density functional (DFT) calculations. Furthermore, electrostatic potential (MEP), natural bonds orbitals (NBO), HOMO–LUMO energies, chemical reactivity descriptors, dipole moment, and Fukui functions of all the urolithins were investigated by resorting the conceptual of DFT at the M06-2X/6-311++G (d, p) basis set as a tool to analyse and comprehend the molecular interaction. The results showed that all the urolithins comply with the Lipinski's rule of five and have biological activity. According to the toxicity predictions, Uro A, Uro C, and Uro D belong to class 4 while Uro B belongs to class 6. The chemical reactivity and stability features of the investigated compounds were evaluated using global chemical reactivity descriptors calculated from the Frontier Molecular Orbitals (FMOs) energies gap, which revealed that the stability order of the molecules was Uro B > Uro C > Uro D > Uro A. The present findings indicate that the urolithins could be a promising candidate for development into a therapeutic medication. Communicated by Ramaswamy H. Sarma