Green Synthesis of New Arylazocoumarins Incorporated with Thiazole Moiety and Their Antimicrobial Activity

Using both conventional and grindstone methods, 2-(thiazol-2-yl)acetonitrile derivatives 3a and 3b reacted with 2-hydroxy-5-(phenyldiazenyl) benzaldehyde derivatives 4a-h to produce new coumarin analogs that included the thiazole moiety 6a-h and 8a-g. Every synthetic compound was evaluated for in vitro antimicrobial activity, with minimum inhibitory concentrations (MICs) determined for the most potent agents. It was found that compounds 8b and 8e showed the highest antibacterial activities against Escherichia coli with diameter of inhibition zone values of 28±0.5 and 28±1, respectively, compared to gentamicin as a reference (27±0.1). Compounds 6b and 8f were the most powerful agents against Acinetobacter baumannii (24±0.5 and 25±1.1, respectively), surpassing tigcycline's activity (23±0.4). In particular, compound 6g was found to be the most potent derivative against Candida albicans with antifungal activity of 26±1 compared to the nystatin drug (28±0.2). The MIC results revealed that most tested compounds matched the efficacy of gentamicin against Escherichia coli, with an MIC of 31.25 μg/ml. Against Klebsiella pneumonia, compounds 6g, 8b, 8f, and 8g exhibited superior MICs of 31.25 μg/ml, outperforming the standard MIC of 62.5 μg/ml. All tested compounds displayed MICs of 31.25 μg/ml, comparable to tigecycline against Acinetobacter baumannii. Notably, compound 6g exhibited strong activity with an MIC of 31.25 μg/ml against Staphylococcus aureus and Streptococcus mutans, exceeding the efficacy of ampicillin (MIC = 62.5 μg/ml). Furthermore, Swiss ADME studies were performed on selected compounds to assess their potential as safe medications by predicting their pharmacokinetic and physicochemical features.