Synthesis of some new 2-(3-pyridyl)-4,5-disubstituted thiazoles as potent antimicrobial agents

As a part of ongoing studies in developing new potent antimicrobial agents, a series of novel 2-(3-pyridyl)-4,5-disubstituted thiazoles was efficiently synthesized and characterized by spectral and elemental analyses. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against ten bacterial and five fungal human pathogenic strains using the disc diffusion assay. Among the synthesized compounds, 5-acetyl-4-methyl-2-(3-pyridyl)thiazole (5) exhibited twofold antibacterial activity of ampicillin in inhibiting the growth of Staphylococcus epidermidis (MIC 0.24 μg/mL) and also showed equipotent antifungal activity with amphotricin B against Geotricum candidum (MIC 0.48 μg/mL). From structure–activity relationship (SAR) point of view, increasing the size of the substitutions either at position 4 or 5 on the thiazole nucleus decreased the antimicrobial activity.

Graphical abstractA series of novel 2-(3-pyridyl)-4,5-disubstituted thiazoles was efficiently synthesized starting from thionicotinitrile to evaluate their antimicrobial activity.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of novel 2-(3-pyridyl)-4,5-disubstituted thiazoles was synthesized and evaluated for their antimicrobial activity. ► Thiazole 5 showed twofold activity of ampicillin against S. epidermidis (MIC 0.24 μg/mL). ► Most of the synthesized thiazoles were found to exhibit in vitro good antifungal activity. ► The attachment of pyridyl moiety to thiazole ring is crucial in developing a new antimicrobial agent. ► Increasing the size of the substituent on the thiazole nucleus decreased the antimicrobial activity.