Synthesis, Biological Activity, and Molecular Docking Study of New Triazoline Derivatives Using 2-Amino-5-p-subtituted Phenyl-1,3,4-thiadiazoles

In this study, new heterocyclic compounds containing 1,3,4-thiadiazole derivatives were synthesized. FT-IR, 1H NMR, and 13C NMR spectroscopy were used to identify the title compounds. In addition, some produced compounds were tested in vitro to assess their antimicrobial effectiveness against various microorganisms such as Escherichia coli and Staphylococcus aureus, demonstrating that some of these compounds exhibit very good antibacterial activity. Molecular docking of some of the synthesized compounds showed good results. 1,3,4-Thiadiazole derivatives (1a, 1b) were prepared by a reaction of p-nitrobenzoic acid or p-toluic acid with thiosemicarbazide in the presence of POCl3. Alkylation of compounds 1a, 1b with allyl bromide produced N-allyl thiadiazoles 2a, 2b. Cyclization of the prepared p-substituted azidobenzene and alkyl azides with compounds 2a, 2b resulted in the corresponding 1,4-disubstituted triazoline derivatives 3a–3h and 4a–4d. Molecular docking studies with the target 6ul7 indicated favorable docking scores and binding interactions for the newly synthesized compounds, highlighting their potential as effective antimicrobial agents.