1. A new small-molecule KRE2 inhibitor against invasive Candida parapsilosis infection.
- Author
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Salci TP, Negri M, R Abadio AK, Bonfim-Mendonça P, Capoci I, Caparroz-Assef SM, Donatti L, S Felipe MS, Kioshima ES, and Svidzinski TI
- Subjects
- Animals, Antifungal Agents therapeutic use, Computer Simulation, Enzyme Inhibitors therapeutic use, Male, Mice, Mice, Inbred BALB C, Antifungal Agents pharmacology, Candida parapsilosis drug effects, Candidiasis, Invasive drug therapy, Enzyme Inhibitors pharmacology, Fungal Proteins antagonists & inhibitors, Mannosyltransferases antagonists & inhibitors
- Abstract
Aim: To investigate the antifungal activity of MOL3, a small molecule that was selected by virtual screening, against Candida spp., Materials & Methods: The antifungal activity of MOL3 was evaluated using standard strains and clinical isolates. Activity was evaluated in both in vitro tests and animal models., Results: The minimum fungicidal concentration of MOL3 against Candida spp. ranged from 16 to 128 mg/l. MOL3 at the sub-minimum fungicidal concentration inhibited hyphal elongation. The remaining yeast cells presented morphological changes and were metabolically inactive. MOL3 was toxicologically inert both in vitro and in the animal model. MOL3 also reduced experimental systemic infection by C. parapsilosis in mice., Conclusion: The selection of MOL3 by virtual screening was successful, revealing a promising antifungal candidate.
- Published
- 2017
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