Brunskole Mojca, Stefane Bogdan, Zorko Karmen, Anderluh Marko, Stojan Jure, Lanisnik Rizner Tea, Gobec Stanislav
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Bioorg Med Chem. 2008 Jun 1;16(11):5881-9. doi: 10.1016/j.bmc.2008.04.066. Epub 2008 Apr 29.
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.
三羟基萘还原酶（3HNR）是真菌黑色素生物合成中的一种关键酶，它是新型杀菌剂和抗真菌剂开发中一个新出现的靶点。为促进新型抑制剂的发现，人们开发了人工底物2,3-二氢-2,5-二羟基-4H-苯并吡喃-4-酮（DDBO）的改进化学合成方法。在来自弯孢霉（一种已知的植物病原体和机会性人类病原体）的3HNR上筛选了一系列化合物，并获得了几种结构多样的活性化合物。弯孢霉3HNR的同源建模可以解释它们的结合模式，并将有助于基于结构进一步设计新的和改进的抑制剂。
