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

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.