The Fungal Phytotoxin Alternariol 9‑Methyl Ether and Some of Its Synthetic Analogues Inhibit the Photosynthetic Electron Transport Chain

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2013-12, Vol.76 (12), p.2234-2245
• Main Authors: Demuner, Antonio Jacinto, Barbosa, Luiz Cláudio Almeida, Miranda, Ana Cristina Mendes, Geraldo, Guilherme Carvalho, da Silva, Cleiton Moreira, Giberti, Samuele, Bertazzini, Michele, Forlani, Giuseppe
• Format: Article
• Language: English
• Subjects: Alternaria; Alternaria - chemistry; Chloroplasts - drug effects; Chloroplasts - metabolism; Chromones - chemical synthesis; Chromones - chemistry; Chromones - pharmacology; Electron Transport - drug effects; Lactones - analysis; Lactones - chemical synthesis; Lactones - chemistry; Lactones - pharmacology; Molecular Structure; Mycotoxins - pharmacology; Oxidation-Reduction; Photosynthesis - drug effects; Pyridones - chemical synthesis; Pyridones - chemistry; Pyridones - pharmacology; Spinacia oleracea; Spinacia oleracea - cytology; Spinacia oleracea - metabolism
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np4005882

Alternariol and monomethylalternariol are natural phytotoxins produced by some fungal strains, such as Nimbya and Alternaria. These substances confer virulence to phytopathogens, yet no information is available concerning their mode of action. Here we show that in the micromolar range alternariol 9-methyl ether is able to inhibit the electron transport chain (IC50 = 29.1 ± 6.5 μM) in isolated spinach chloroplasts. Since its effectiveness is limited by poor solubility in water, several alternariol analogues were synthesized using different aromatic aldehydes. The synthesized 6H-benzo[c]cromen-6-ones, 5H-chromene[4,3-b]pyridin-5-one, and 5H-chromene[4,3-c]pyridin-5-one also showed inhibitory properties, and three 6H-benzo[c]cromen-6-ones were more effective (IC50 = 12.8–22.8 μM) than the lead compound. Their addition to the culture medium of a cyanobacterial model strain was found to inhibit algal growth, with a relative effectiveness that was consistent with their activity in vitro. In contrast, the growth of a nonphotosynthetic plant cell culture was poorly affected. These compounds may represent a novel lead for the development of new active principles targeting photosynthesis.