Platform for Unique Models Application (P.U.M.A), Department of Pharmaceutical Microbiology and Parasitology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Department of Organic Chemistry and Drug Technology, Faculty of Pharmacy, Wroclaw Medical University, 211A Borowska Street, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2023 Nov 7;24(22):16033. doi: 10.3390/ijms242216033.
The distinct structure of cationic organic compounds plays a pivotal role in enhancing their water solubility, which in turn influences their bioavailability. A representative of these compounds, which contains a delocalized charge, is 5-amino-2-(5-amino-3-methyl-1,2-oxazol-4-yl)-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-ylium bromide (ED). The high-water solubility of ED obviates the need for potentially harmful solvents during in vitro testing. The antibacterial and antifungal activities of the ED compound were assessed in vitro using the microtiter plate method and a biocellulose-based biofilm model. Additionally, its cytotoxic effects on wound bed fibroblasts and keratinocytes were examined. The antistaphylococcal activity of ED was also evaluated using an in vivo larvae model of . Results indicated that ED was more effective against Gram-positive bacteria than Gram-negative ones, exhibiting bactericidal properties. Furthermore, ED demonstrated greater efficacy against biofilms formed by Gram-positive bacteria. At bactericidal concentrations, ED was non-cytotoxic to fibroblasts and keratinocytes. In in vivo tests, ED was non-toxic to the larvae. When co-injected with a high load of , it reduced the average larval mortality by approximately 40%. These findings suggest that ED holds promise for further evaluation as a potential treatment for biofilm-based wound infections, especially those caused by Gram-positive pathogens like .
阳离子有机化合物独特的结构在提高其水溶性方面起着关键作用，而水溶性又会影响其生物利用度。具有离域电荷的此类化合物的一个代表是 5-氨基-2-(5-氨基-3-甲基-1,2-恶唑-4-基)-3-甲基-2,3-二氢-1,3,4-恶二唑-2-鎓溴化物（ED）。ED 的高水溶性使得在体外测试过程中无需使用潜在有害的溶剂。采用微量滴定板法和基于生物纤维素的生物膜模型，评估了 ED 化合物的体外抗菌和抗真菌活性。此外，还研究了其对创面成纤维细胞和角质形成细胞的细胞毒性作用。还使用金黄色葡萄球菌幼虫模型评估了 ED 的抗葡萄球菌活性。结果表明，ED 对革兰氏阳性菌的活性比对革兰氏阴性菌更强，具有杀菌特性。此外，ED 对革兰氏阳性菌形成的生物膜更有效。在杀菌浓度下，ED 对成纤维细胞和角质形成细胞无细胞毒性。在体内试验中，ED 对幼虫无毒。当与高负荷 共同注射时，它使幼虫的平均死亡率降低了约 40%。这些发现表明 ED 有望进一步评估为治疗生物膜相关创面感染的潜在药物，特别是由金黄色葡萄球菌等革兰氏阳性病原体引起的感染。
