Synthesis, characterization, crystal structure, DFT, HSA, ADMET prediction and antibacterial activity of thiohydantoin analogues

In this research, we explore the synthesis and pharmacological evaluation of novel heterocyclic molecules, drawing inspiration from certain drugs, specifically thiophenytoin. A batch of thiohydantoin derivatives 2a-2f were synthesized and characterized by FT-IR, 1H NMR, 13C NMR and Mass spectrometry. Compound 2b was also characterized by XR-Diffraction. Then, we evaluated the antibacterial activity in vitro against three strains Rhodococcus equi, Rhodococcus sp GK1 and Rhodococcus sp GK3. Compounds 1 and 2a-f showed similar efficacy compared to the commercial antibiotic chloramphenicol in trials against Rhodococcus equi and Rhodococcus sp GK1. Moreover, derivatives of compound 2, which were alkylated with methyl (2a), propyl (2c), butyl (2d), pentyl (2e), and benzyl (2f) groups, showed significant antibacterial activity against the Rhodococcus sp GK3 strain. Additionally, the molecular structure of 2b was examined through Hirshfeld surface analysis (HSA), density functional theory (DFT) calculations and Molecular Electrostatic Potential (MEP) study. Enabling the identification of electrophilic, nucleophilic centers and predict potential intermolecular interactions. Finally, ADMET studies were conducted to explore the pharmacokinetics of the title compounds as antibacterial drugs.