Exploring Novel Cyclopropyl conjoined 1,3‐Thiazole‐2‐imines Derivatives as Multi‐Target Agents: Design, Synthesis, Biological Evaluation, DFT, Molecular Docking, and ADMET Studies

In the present work, we developed a library of novel cyclopropyl clubbed 1,3‐thiazole‐2‐imines (6a‐h) from the efficient cyclization between multistep synthesized thiourea precursors and ethyl 2‐chloroacetoacetate. Subsequently, the in vitro biological screening including antibacterial, α‐amylase, and proteinase K inhibition was carried out to assess their inhibition potential. In general, all synthesized compounds revealed moderate to significant potency. The compound (6a) with no substitution at the phenyl ring exhibited the highest inhibitory activity amongst all, with an IC50 value of 1.716 ± 0.062 µM against proteinase K. Fortunately, this compound (6a) also unfolded the most significant antibacterial potential against B. subtilis showing 20 mm zone of inhibition. The compound (6d) possessing a naphthyl ring was found to be the most potent inhibitor of amylase displaying IC50 value of 1.634 ± 0.002 µM. Diverse substitution patterns on 2‐imino‐1,3‐thiazoline pharmacophores provided a valuable basis for SAR analysis. Computational studies including DFT, molecular electrostatic potential, molecular docking, and ADMET were conducted to predict the chemical reactivity, ligand‐protein binding interactions, and drug‐likeness of synthesized compounds. Hence these studies highlighted our synthesized compounds as novel antibacterial, α‐amylase, and proteinase K inhibitors.