Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien 9-Bancho, Nishinomiya 663-8179, Hyogo, Japan.
Institute for Women's Career Advancement and Gender Equality Development, Mukogawa Women's University, 6-46 Ikebiraki, Nishinomiya 663-8558, Hyogo, Japan.
Molecules. 2024 Mar 13;29(6):1277. doi: 10.3390/molecules29061277.
There is an urgent need to discover and develop novel antibacterial agents. Accordingly, we synthesised 2-(piperazin-1-yl)naphtho[2,3-d]thiazole-4,9-dione (PNT), which exhibits antimicrobial activity. The aim of this study was to characterise PNT as an effective antimicrobial agent. Fluorescence microscopy was used to measure PNT's uptake into microbial cells (strains of , , and methicillin-resistant (MRSA)), transmission electron microscopy (TEM) was used to investigate the influence of PNT on the configuration of microbial cells, and a DNA gyrase supercoiling assay was used to investigate whether PNT inhibits DNA gyrase. PNT was taken up by more than 50% of microbial cells within 30 min. Using TEM, hollowed-out bacterial cytoplasms were observed in the specimen treated with PNT, although there was no disintegration of the bacterial membrane. In the DNA gyrase supercoiling assay, a dose-dependent reduction in fluorescence intensity was observed as the concentration of PNT increased. This suggests that PNT is taken up by microbial cells, resulting in cell disruption, and it reveals that one of the mechanisms underlying the antimicrobial activity of PNT is the inhibition of DNA gyrase.
目前迫切需要发现和开发新型抗菌剂。为此，我们合成了具有抗菌活性的 2-(哌嗪-1-基)萘并[2,3-d]噻唑-4,9-二酮（PNT）。本研究旨在将 PNT 确认为一种有效的抗菌剂。荧光显微镜用于测量 PNT 进入微生物细胞（ 、 和耐甲氧西林金黄色葡萄球菌（MRSA）菌株）的摄取情况，透射电子显微镜（TEM）用于研究 PNT 对微生物细胞结构的影响，而 DNA 拓扑异构酶超螺旋化实验用于研究 PNT 是否抑制 DNA 拓扑异构酶。在 30 分钟内，超过 50%的微生物细胞摄取了 PNT。使用 TEM，在经 PNT 处理的标本中观察到了中空的细菌细胞质，尽管细菌膜没有破裂。在 DNA 拓扑异构酶超螺旋化实验中，随着 PNT 浓度的增加，荧光强度呈剂量依赖性降低。这表明 PNT 被微生物细胞摄取，导致细胞破裂，并揭示了 PNT 抗菌活性的机制之一是抑制 DNA 拓扑异构酶。
