Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action

• Main Authors: Fangfang Tan, Baojun Shi, Jian Li, Wenjun Wu, Jiwen Zhang
• Format: Article
• Language: English
• Published: MDPI AG 2015-11-01
• Series: Molecules
• Subjects: synthesis; 4,5-dihydrothiazole; antibacterial activity; antibacterial mechanism
• Online Access: http://www.mdpi.com/1420-3049/20/11/19680

Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S)-2-(2′-hydroxyphenyl)-4-hydroxy-methyl- 4,5-dihydrothiazole (7h) and (R)-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydro-thiazole (7h′) exhibited significant inhibition against Ralstonia solanacearum, Pseudomonas syringae pv. actinidiae, Bacillus subtilis and Bacillus cereus, with minimum inhibitory concentrations (MICs) ranging from 3.91 to 31.24 μg·mL−1. The effect of substituents showed that not only electron-withdrawing groups, but also electron-donating groups could abolish the antibacterial activities unless a 2′-hydroxy group was introduced on the 2-aryl substituent of the 4,5-dihydrothiazole analogues. The results of scanning electron microscope (SEM) and fatty acid exposure experiments indicated that these antibacterial compounds influence fatty acid synthesis in the tested bacteria.