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.
Highlights
Invasive candidiasis has been considered a significant reason of death in immuno-compromised and critically ill patients[1–6]
Invasive candidiasis can initially be managed in critically ill patients by utilizing an echinocandin, e.g. caspofungin[7,8]
Caspofungin inhibits the enzyme b(1,3)-D-glucan synthase of the fungal cell wall in a non-competitive manner leading to inhibition of the synthesis of b(1,3)-D-glucan. b(1,3)-D-glucan is a crucial element of the cell wall of many fungal species and forms a solid three-dimensional matrix that is involved in shape determination and mechanical strength of the cell wall[9,10]
Summary
Invasive candidiasis has been considered a significant reason of death in immuno-compromised and critically ill patients[1–6]. Invasive candidiasis can initially be managed in critically ill patients by utilizing an echinocandin, e.g. caspofungin[7,8]. Caspofungin inhibits the enzyme b(1,3)-D-glucan synthase of the fungal cell wall in a non-competitive manner leading to inhibition of the synthesis of b(1,3)-D-glucan. B(1,3)-D-glucan is a crucial element of the cell wall of many fungal species and forms a solid three-dimensional matrix that is involved in shape determination and mechanical strength of the cell wall[9,10]. Inhibiting the synthesis of b(1,3)-D-glucan has both fungistatic and fungicidal outcomes. 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 b(1,3)-D-glucan synthase of the fungal cell wall. Results: Considering the hydrogen bond analysis, two compounds (ZINC71336662 and ZINC40910772) were predicted to better interact with the active site of b(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
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