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Bacterial strains that produce New Delhi metal-β-lactamase 1 (NDM-1) are a worldwide health threat. It remains a challenging task to find a potent NDM-1 inhibitor for clinical practice.Molecular docking and virtual screening of an in-house fungal natural product database for NDM-1 inhibitors were performed. Based on the screening results, the affinity and inhibition ability of potential NDM-1 inhibitors were determined using purified NDM-1. The efficacy of compounds in combination with four β-lactam antibiotics (meropenem, imipenem, ceftriaxone and ampicillin) was evaluated. Morphological changes in Klebsiella pneumoniae ATCC BAA-2146 after treatment with the compounds were visualised by transmission electron microscopy.In silico screening led to the identification of four fungal products as potential NDM-1 inhibitors. Emerione A (1), a methylated polyketide with bicyclo[4.2.0]octene and 3,6-dioxabicyclo[3.1.0]hexane functionalities, has significant activity in cells (KConsidering the low toxicity of emerione A (1), it may represent a potential lead compound for anti-NDM-1 drug development. |
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