Details

Autor(en) / Beteiligte

• Fehr, Marcus
• Koch, Andreas
• Merget, Benjamin
• Winter, Christian

Titel

Quinazolinone Alkaloid Febrifugine and Its Analogues To Control Phytopathogenic Diseases Caused by Oomycete Fungi

Ist Teil von

• European journal of organic chemistry, 2022-04, Vol.2022 (13), p.n/a

Ort / Verlag

Weinheim: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Controlling phytopathogenic diseases caused by oomycete fungi is still a challenge in crop protection research. Studies on identifying new starting points to control phytopathogens revealed that the quinazolinone alkaloids febrifugine (1) and halofuginone (2) are efficiently inhibiting the growth of Phytophthora infestans in microtiter tests. However, despite the very good in vitro activity of 0.13 and 0.06 ppm in IC50, respectively, both compounds did not exhibit a good control of P. infestans on tomato plants. Creating a homology model of prolyl‐tRNA synthetase – the molecular target of halofuginone – helped to understand the interactions between 2 and the binding pocket and guided the synthesis of further derivatives. Ultimately, we found that deoxy‐febrifugine (14) and halofuginol (17) and its derivatives were able to control P. infestans also on the plant. Small‐molecule natural products are often attractive antifungal starting points that spark further synthesis for ligand optimization. Febrifugine and halofuginone were identified as potent in vitro inhibitors of late blight (Phytophthora infestans). Guided by structure‐based design, several derivatives were synthesized and tested. By targeted modification of two structural features, control of P. infestans was obtained also on the plant.