{"title":"Virtual screening for potential inhibitors of β(1,3)-D-glucan synthase as drug candidates against fungal cell wall.","authors":"Zinat Farhadi, Tayebeh Farhadi, Seyed MohammadReza Hashemian","doi":"10.1080/21556660.2020.1734010","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> The introduced compound in this study may be valuable to analyze experimentally as a novel oral drug candidate targeting fungal cell walls.</p>","PeriodicalId":15631,"journal":{"name":"Journal of Drug Assessment","volume":"9 1","pages":"52-59"},"PeriodicalIF":2.4000,"publicationDate":"2020-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21556660.2020.1734010","citationCount":"7","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Assessment","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21556660.2020.1734010","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 7
Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: The introduced compound in this study may be valuable to analyze experimentally as a novel oral drug candidate targeting fungal cell walls.
背景:为了提高侵袭性念珠菌病患者的预后,有必要开始适当剂量的有效抗真菌治疗。棘白菌素(如caspofungin)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,棘白菌素对人体的不良反应和毒性较低。棘白菌素有注射(静脉注射)形式。方法:为了鉴定影响真菌细胞壁的新型口服药物样化合物,本研究采用虚拟筛选程序对锌数据库中下载的口服药物样化合物进行处理。计算了对接自由能,并与已知抑制剂caspofungin进行了比较。选择四个分子作为最有效的配体并进行氢键分析。结果:结合氢键分析,预测ZINC71336662和ZINC40910772两种化合物与β(1,3)- d -葡聚糖合成酶活性位点的相互作用优于caspofungin。结论:该化合物可作为一种靶向真菌细胞壁的新型口服药物进行实验分析。