Bhattacharyya Anamika, Sinha Mau, Singh Himanshi, Patel Ranjeet Singh, Ghosh Sumana, Sardana Kabir, Ghosh Shamik, Sengupta Shiladitya
Vyome Therapeutics Ltd., New Delhi, India.
Department of Dermatology, Atal Bihari Vajpayee Institute of Medical Sciences, Dr. Ram Manohar Lohia Hospital, New Delhi, India.
Front Microbiol. 2020 Sep 8;11:2116. doi: 10.3389/fmicb.2020.02116. eCollection 2020.
The prevalence of drug-resistant pathogenic fungi is a major global health challenge. There is an urgent need for novel drugs that can exert a potent antifungal activity and overcome resistance. Newly discovered anti-fungal properties of existing compounds can potentially offer a rapid solution to address this persistent threat. We rationalized that structures which disrupt the fungal cell membrane could address the above unmet need. As fatty acids underpin the formation and stability of cell membranes, we used computational simulations to evaluate the interactions between selected short chain fatty acids and a model cell membrane. Here, we report that caprylic acid could penetrate and perturb the membrane . Based on the findings, we identified a derivative of this fatty acid that disrupts fungal membranes as detected using steady-state fluorescence anisotropy. We show that this fatty acid derivative is potent against a variety of fungal pathogens like and . We further demonstrated the ability of this fatty acid derivative to potentiate some azoles and enhance the efficacy of antifungal formulations Our data suggests the emergence of a novel therapy for effective disease management and overcoming anti-fungal drug resistance.
耐药致病真菌的流行是一项重大的全球健康挑战。迫切需要能够发挥强大抗真菌活性并克服耐药性的新型药物。现有化合物新发现的抗真菌特性有可能为应对这一持续威胁提供快速解决方案。我们推断，破坏真菌细胞膜的结构可以满足上述未满足的需求。由于脂肪酸是细胞膜形成和稳定性的基础，我们使用计算模拟来评估选定的短链脂肪酸与模型细胞膜之间的相互作用。在此，我们报告辛酸可以穿透并扰乱膜。基于这些发现，我们鉴定出这种脂肪酸的一种衍生物，使用稳态荧光各向异性检测发现它会破坏真菌膜。我们表明这种脂肪酸衍生物对多种真菌病原体如……有效。我们进一步证明了这种脂肪酸衍生物增强某些唑类药物并提高抗真菌制剂疗效的能力。我们的数据表明出现了一种用于有效疾病管理和克服抗真菌耐药性的新疗法。
