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

Abstract

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.

DOI: 10.1016/j.bmc.2008.04.066

Cite this paper

@article{Brunskole2008TowardsTF, title={Towards the first inhibitors of trihydroxynaphthalene reductase from Curvularia lunata: synthesis of artificial substrate, homology modelling and initial screening.}, author={Mojca Brunskole and Bogdan Stefane and Karmen Zorko and Marko Anderluh and Jure Stojan and Tea Lani{\vs}nik Ri{\vz}ner and Stanislav Gobec}, journal={Bioorganic & medicinal chemistry}, year={2008}, volume={16 11}, pages={5881-9} }