Aim: The shape-based virtual screening was used for the identification of new compounds anti-paracoccidioidomycosis (PCM).
Materials & methods: The study was performed according to the following steps: collection and curation of a dataset of quinolinyl N-oxide chalcones with anti-PCM activity, development and validation of shape-based models, application of the best model for virtual screening, and experimental validation.
Results & conclusion: Among 31 computational hits, eight compounds showed potent antifungal activity and low cytotoxicity for mammalian cells. The checkerboard assay showed that most promising hit (compound 3) displayed additive effects with the antifungal cotrimoxazole and amphotericin B. Therefore, the shape-based virtual screening allowed us to discover promising compounds in prospective hit-to-lead optimization studies for tackling PCM.
Keywords: 5-nitroheteroaryl chalcones; antifungal activity; computer-aided drug design; paracoccidioidomycosis; shape-based.