Multifaceted exploration of acylthiourea compounds: In vitro cytotoxicity, DFT calculations, molecular docking and dynamics simulation studies

Int J Biol Macromol. 2024 Oct;278(Pt 3):134870. doi: 10.1016/j.ijbiomac.2024.134870. Epub 2024 Aug 22.

Abstract

This study reports the synthesis and analysis of biologically active acylthiourea compounds (1 and 2) with a cyclohexyl moiety. The compounds were characterized using UV-Visible, FT-IR, 1H/13C NMR, and elemental analysis. The crystal structure of 2 was solved, revealing intra- and inter-molecular hydrogen bonds. Density functional theory (DFT) calculations provided insights into chemical reactivity and non-covalent interactions. Cytotoxicity assays showed the cyclohexyl group enhanced the activity of compound 2 compared to compound 1. Epoxide hydrolase 1 was predicted as the enzyme target for both compounds. We modeled the structure of epoxide hydrolase 1 and performed molecular dynamics simulation and docking studies. Additionally, in silico docking with SARS-CoV-2 main protease, human ACE2, and avian influenza H5N1 hemagglutinin indicated strong binding potential of the compounds. This integrated approach improves our understanding of the biological potential of acylthiourea derivatives.

Keywords: ACE2; Acylthiourea; Avian influenza H5N1 hemagglutinin; Cytotoxicity; Epoxide hydrolase 1; Molecular dynamics simulation; SARS-CoV-2 main protease.

MeSH terms

  • Density Functional Theory*
  • Epoxide Hydrolases / antagonists & inhibitors
  • Epoxide Hydrolases / chemistry
  • Epoxide Hydrolases / metabolism
  • Humans
  • Hydrogen Bonding
  • Influenza A Virus, H5N1 Subtype / drug effects
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • SARS-CoV-2 / drug effects
  • Thiourea* / analogs & derivatives
  • Thiourea* / chemistry
  • Thiourea* / pharmacology

Substances

  • Thiourea
  • Epoxide Hydrolases