Jain Tushar, Muktapuram Pratap Reddy, Pochampalli Satyanarayana, Sharma Komal, Pant Garima, Mitra Kalyan, Bathula Surendar Reddy, Banerjee Dibyendu
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow-226 031, U.P., India.
Academy of Scientific & Innovative Research, Chennai-600113, India.
J Med Microbiol. 2017 Dec;66(12):1706-1714. doi: 10.1099/jmm.0.000610. Epub 2017 Oct 27.
Candida species have become resistant to commonly used anti-fungal drugs like fluconazole and echinocandins. In our screen, a series of quaternary ammonium compounds (QACs) emerged as an alternative treatment choice for drug-resistant Candida infections.
Medium alkyl chain cationic lipo-oxazoles comprising six to thirteen twin carbon chains and a quaternary ammonium unit were synthesized and evaluated for their in vitro anti-Candida and biofilm inhibition activity. SEM was performed to visualize membrane distortion.Results/Key findings. Heptyl and octyl chain analogues (5c, 6b and 6c) showed promising anti-fungal activity. Compound 5c was active against both fluconazole-sensitive and resistant clinical isolates of Candida albicans as well as non-albicans Candida strains. 5c also inhibited the adhesion of C. albicans cells to a polystyrene surface and restricted biofilm formation. SEM further confirmed Candida cell membrane distortion by 5c.
A novel class of QACs, called cationic lipo-oxazoles, was tested and found to exhibit anti-fungal activity against planktonic cells as well as biofilms of Candida.
念珠菌属已对氟康唑和棘白菌素等常用抗真菌药物产生耐药性。在我们的筛选中，一系列季铵化合物（QACs）成为耐药念珠菌感染的替代治疗选择。
合成了包含六至十三条孪碳链和一个季铵单元的中等烷基链阳离子脂氧唑，并评估其体外抗念珠菌和生物膜抑制活性。进行扫描电子显微镜（SEM）观察膜变形情况。
结果/主要发现：庚基和辛基链类似物（5c、6b和6c）显示出有前景的抗真菌活性。化合物5c对白色念珠菌的氟康唑敏感和耐药临床分离株以及非白色念珠菌菌株均有活性。5c还抑制白色念珠菌细胞对聚苯乙烯表面的粘附并限制生物膜形成。扫描电子显微镜进一步证实5c可使念珠菌细胞膜变形。
测试了一类名为阳离子脂氧唑的新型季铵化合物，发现其对念珠菌的浮游细胞以及生物膜均具有抗真菌活性。
