Design, Synthesis, Characterization, Evaluation Antimicrobial Evaluation of 2 – Amino Thiazole Based Lead Compound : Docking Analysis of Ortho and Meta Substituted Analogues

The present study reports the design, synthesis and antimicrobial evaluation of a 2-aminothiazole based scaffold alongside docking analysis of its ortho and meta substituted analogues. Given their wide range of pharmacological activities, 2-amino thiazole derivatives continue to serve as valuable templates in the search for novel antimicrobial agents. A retrosynthetic plan was generated using IBM RXN software, and the compound was synthesised through a diazotization reaction involving 2 amino thiazole, phenol, sodium nitrite and acetic acid, with sodium hydroxide (NaOH) for pH adjustment. The product was soluble in dimethyl sulfoxide (DMSO), and ethanol. Structural characterization was achieved through Uv-Vis (Ultraviolet Visible Spectroscopy), FTIR (Fourier Transform Infrared Spectroscopy), NMR (Nuclear Magnetic Resonance Spectroscopy), and Mass Spectrometry, confirming the expected aromatic and phenolic functionalities. Antimicrobial screening using agar well diffusion method against Staphylococcus aureus and Escherichia coli demonstrated moderate inhibitory activity. The results revealed a maximum docking score of -7.98 kcal/mol, which although close, did not cross the threshold for strong binding (≤-8.0 kcal/mol). In conclusion, the synthesised compound exhibits antimicrobial activity but limited binding affinity in docking analysis. These findings indicate that additional structural modifications are necessary to enhance lead optimization and binding interactions, highlighting the combined importance of synthetic biological, and computational approaches in drug discovery.