Towards the first inhibitors of trihydroxynaphthalene reductase from Curvularia lunata: Synthesis of artificial substrate, homology modelling and initial screening

Trihydroxynaphthalene reductase (3HNR) is an essential enzyme in the biosynthesis of fungal melanin and it represents an emerging target for the development of new fungicides and antimicotics. To promote the discovery of new inhibitors, an improved chemical synthesis of the artificial substrate 2,3-dihydro-2,5-dihydroxy-4H-benzopyran-4-one (DDBO) was developed. A series of compounds were screened on 3HNR from Curvularia lunata, a known plant pathogen and an opportunistic human pathogen, and several structurally diverse hits were obtained. Homology modelling of 3HNR from C. lunata can explain their binding modes and will enable further structure-based design of new and improved inhibitors.

A series of compounds were screened on trihydroxynaphthalene reductase from Curvularia lunata, a known plant pathogen and an opportunistic human pathogen, and several structurally diverse hits were obtained. Homology model of the enzyme was built to enable further structure-based design of new and improved inhibitors.Figure optionsDownload as PowerPoint slide