水溶性制霉菌素及其衍生物。
Water-Soluble Nystatin and Derivative.
作者信息
Amir Aviran, Levin-Khalifa Michal, Dvash Tamar
机构信息
MilliporeSigma life science, Kiryat Hamada 13, 9777613 Jerusalem, Israel.
出版信息
ACS Med Chem Lett. 2022 Jan 20;13(2):182-187. doi: 10.1021/acsmedchemlett.1c00538. eCollection 2022 Feb 10.
Fungal infections are increasingly causing more morbidity and mortality, especially for immunocompromised people. In recent years, there is growing evidence that new medicine-resistant fungal strains are posing added challenges in the clinic. Nystatin is a known antifungal from the polyene family. Due to Nystatin limited solubility and high toxicity, it is used mainly to treat oral and dermal fungal infections. In search for new Nystatin derivatives and formulations, we obtained amide derivatives and a deoxycholate formulation that were not described previously for this compound. Furthermore, we tested the potency of the derivatives and formulation by the USP(81) method and minimum inhibitory concentration of and . Additionally, the in vitro toxicity and stability were tested, and it was found that the ethanol amide derivative of Nystatin was fully water-soluble (up to 100 mg/mL) with the same potency of Nystatin but with 13.5 times lower toxicity. The ethanol amide derivative of Nystatin is a promising candidate for future drug development.
真菌感染正日益导致更多的发病和死亡，尤其是对免疫功能低下的人群。近年来，越来越多的证据表明，新型耐药真菌菌株给临床带来了更多挑战。制霉菌素是一种已知的来自多烯家族的抗真菌药物。由于制霉菌素溶解度有限且毒性高，它主要用于治疗口腔和皮肤真菌感染。为了寻找新的制霉菌素衍生物和制剂，我们获得了酰胺衍生物和一种脱氧胆酸盐制剂，此前尚未有关于该化合物的此类描述。此外，我们通过美国药典（81）方法以及[具体物质]的最低抑菌浓度测试了衍生物和制剂的效力。另外，还测试了体外毒性和稳定性，结果发现制霉菌素的乙醇酰胺衍生物完全可溶于水（高达100 mg/mL），其效力与制霉菌素相同，但毒性低13.5倍。制霉菌素的乙醇酰胺衍生物是未来药物开发的一个有前景的候选物。
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