Farhadi Zinat, Farhadi Tayebeh, Hashemian Seyed MohammadReza
Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Behavioral Disease Counseling Center, Marvdasht Health Center, Shiraz University of Medical Sciences, Shiraz, Iran.
J Drug Assess. 2020 Mar 11;9(1):52-59. doi: 10.1080/21556660.2020.1734010. eCollection 2020.
To enhance the outcome in patients with invasive candidiasis, initiation of an efficient antifungal treatment in a suitable dosage is necessary. Echinocandins (e.g. caspofungin) inhibit the enzyme β(1,3)-D-glucan synthase of the fungal cell wall. Compared to azoles and other antifungal agents, echinocandins have lower adverse effects and toxicity in humans. Echinocandins are available in injectable (intravenous) form. In this study, to identify the novel oral drug-like compounds that affect the fungal cell wall, downloaded oral drug-like compounds from the ZINC database were processed with a virtual screening procedure. The docking free energies were calculated and compared with the known inhibitor caspofungin. Four molecules were selected as the most potent ligands and subjected to hydrogen bonds analysis. Considering the hydrogen bond analysis, two compounds (ZINC71336662 and ZINC40910772) were predicted to better interact with the active site of β(1,3)-D-glucan synthase compared with caspofungin. The introduced compound in this study may be valuable to analyze experimentally as a novel oral drug candidate targeting fungal cell walls.
为提高侵袭性念珠菌病患者的治疗效果，必须以合适的剂量开始有效的抗真菌治疗。棘白菌素类药物（如卡泊芬净）可抑制真菌细胞壁的β(1,3)-D-葡聚糖合成酶。与唑类和其他抗真菌药物相比，棘白菌素类药物对人体的不良反应和毒性较低。棘白菌素类药物有注射（静脉注射）剂型。在本研究中，为鉴定影响真菌细胞壁的新型口服类药物化合物，对从ZINC数据库下载的口服类药物化合物进行了虚拟筛选程序处理。计算对接自由能，并与已知抑制剂卡泊芬净进行比较。选择了四个分子作为最有效的配体，并进行氢键分析。考虑到氢键分析，预测两种化合物（ZINC71336662和ZINC40910772）与β(1,3)-D-葡聚糖合成酶活性位点的相互作用比卡泊芬净更好。本研究中引入的化合物作为一种靶向真菌细胞壁的新型口服药物候选物，可能具有重要的实验分析价值。
