选定的 N-萜基有机硒化合物在体外和外阴阴道念珠菌病小鼠模型中具有抗真菌活性。
Selected N-Terpenyl Organoselenium Compounds Possess Antimycotic Activity In Vitro and in a Mouse Model of Vulvovaginal Candidiasis.
发表日期:2023 Oct 31
作者:
Xiuyi Liang, Agata J Pacuła-Miszewska, Magdalena Obieziurska-Fabisiak, Richa Vartak, Ganming Mao, Ketankumar Patel, Natalya U Fedosova, Jacek Ścianowski, Blase Billack
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
在本工作中,通过测定氟康唑 (FLU) 敏感型 (S1) 和 FLU 耐药型 (S1) 中每种化合物的最低抑菌浓度 (MIC),评估了一系列 N-萜基有机硒化合物 (CHB1-6) 的抗真菌活性。 S2)白色念珠菌(C. albicans)菌株。 MIC 筛选中最活跃的化合物是 CHB4 和 CHB6,随后评估了它们在人宫颈癌细胞 (KB-3-1) 中的细胞毒性,发现对真菌具有选择性。接下来,使用重建的 3D 人类表皮研究 CHB4 和 CHB6 的皮肤刺激性,这两种化合物被认为对表皮是安全的。使用外阴阴道念珠菌病 (VVC) 小鼠模型,CHB4 和 CHB6 均通过减少阴道酵母菌定植、减轻对阴道粘膜的损伤以及降低组织中髓过氧化物酶 (MPO) 表达的丰度而表现出抗真菌功效,这表明减少炎症反应。总之,CHB4 和 CHB6 在体外和 VVC 小鼠模型中表现出抗真菌活性,代表了两种新的有前途的抗真菌药物。
In the present work, a series of N-terpenyl organoselenium compounds (CHB1-6) were evaluated for antimycotic activity by determining the minimum inhibitory concentration (MIC) for each compound in fluconazole (FLU)-sensitive (S1) and FLU-resistant (S2) strains of Candida albicans (C. albicans). The most active compounds in the MIC screen were CHB4 and CHB6, which were then evaluated for cytotoxicity in human cervical cancer cells (KB-3-1) and found to be selective for fungi. Next, CHB4 and CHB6 were investigated for skin irritation using a reconstructed 3D human epidermis and both compounds were considered safe to the epidermis. Using a mouse model of vulvovaginal candidiasis (VVC), CHB4 and CHB6 both exhibited antimycotic efficacy by reducing yeast colonization of the vaginal tract, alleviating injury to the vaginal mucosa, and decreasing the abundance of myeloperoxidase (MPO) expression in the tissue, indicating a reduced inflammatory response. In conclusion, CHB4 and CHB6 demonstrate antifungal activity in vitro and in the mouse model of VVC and represent two new promising antifungal agents.