Synthesis and Biological Evaluation of New 3-Phenylthiazolidin-4-One and 3-Phenylthiazole Derivatives as Antimicrobial Agents

A new series of 3-phenylthiazolidin-4-ones <b>4a-h</b> and 3-phenylthiazoles <b>6a-i</b> were synthesized from the reaction of different 4-phenyl-3-thiosemicarbazone derivatives <b>3a-i</b> with dimethyl acetylenedicarboxylate and 4-bromophenacyl bromide, respectively. Preparation of 3-phenylthiazoles <b>6a-i</b> starting from 4-bromophenacyl bromide could be achieved through two pathways either directly or indirectly in which new intermediates <b>5a-i</b> were isolated. The <i>in vitro</i> antibacterial activities of the newly synthesized compounds were tested versus two panels of Gram-positive bacteria; (<i>Staphylococcus aureus</i>, <i>Bacillus subtilis</i>) and Gram-negative bacteria (<i>Escherichia coli</i>, <i>Pseudomonas aeuroginosa</i>). Also, these compounds were tested for their activities as anti-fungal versus a panel of two fungi (<i>Aspergillus flavus</i>, <i>Candida albicans</i>). Compounds <b>4d, 6a, 6d,</b> and <b>6f</b> showed excellent antimicrobial activity exceeded 90%. Compound <b>6d</b> had equivalent potency to Ampicillin in inhibiting the growth of (<i>Bacillus subtilis</i>) bacteria (% activity index= 100%). Most of the rest of compounds showed good antimicrobial activity (70–90%).

本研究分别以不同的4-苯基-3-氨基硫脲衍生物（4-phenyl-3-thiosemicarbazone derivatives）<b>3a-i</b>与乙酰二羧酸二甲酯（dimethyl acetylenedicarboxylate）、4-溴苯甲酰溴（4-bromophenacyl bromide）反应，合成了全新的3-苯基噻唑烷-4-酮（3-phenylthiazolidin-4-ones）<b>4a-h</b>与3-苯基噻唑（3-phenylthiazoles）<b>6a-i</b>系列化合物。以4-溴苯甲酰溴为起始原料制备3-苯基噻唑<b>6a-i</b>时，可通过直接法与间接法两条路径完成，其中间接法可分离得到全新的中间体<b>5a-i</b>。对上述新合成化合物开展了<i>体外（in vitro）</i>抗菌活性测试，受试菌株分为两类：革兰氏阳性菌（Gram-positive bacteria）包括<i>金黄色葡萄球菌（Staphylococcus aureus）</i>与<i>枯草芽孢杆菌（Bacillus subtilis）</i>；革兰氏阴性菌（Gram-negative bacteria）包括<i>大肠杆菌（Escherichia coli）</i>与<i>铜绿假单胞菌（Pseudomonas aeuroginosa）</i>。同时，针对两类受试真菌——<i>黄曲霉（Aspergillus flavus）</i>与<i>白色念珠菌（Candida albicans）</i>，测试了这些化合物的抗真菌活性。测试结果显示，化合物<b>4d</b>、<b>6a</b>、<b>6d</b>与<b>6f</b>展现出优异的抗菌活性，抑菌率超过90%。其中化合物<b>6d</b>在抑制<i>枯草芽孢杆菌（Bacillus subtilis）</i>生长方面的活性与氨苄青霉素（Ampicillin）相当，活性指数达100%。其余多数化合物均表现出良好的抗菌活性，抑菌率介于70%至90%之间。