Strepimidazoles A-G from the Plant Endophytic Streptomyces sp. PKU-EA00015 with Inhibitory Activities against a Plant Pathogenic Fungus

Seven new 4-acyl-2-aminoimidazoles, designated strepimidazoles A-G (1-7), were discovered from the endophytic Streptomyces sp. PKU-EA00015 isolated from Salvia miltiorrhiza Bunge, whose dry root Danshen is one of the most widely used traditional Chinese medicines. The resonance signals of the 2-aminoimidazole moiety in 1-7 were absent in the NMR spectra due to tautomerization, and the structures of 1-7 were identified after preparation of their acetylation products 1a-7a, respectively. Compounds 1-7 represent a new family of 2-aminoimidazole-containing natural products, enriching the structural diversity of natural products from endophytic origin. Compounds 1-7 showed different degrees of inhibitory activities against the plant pathogenic fungus Verticillium dahliae V991, revealing structure-activity relationships on the acyl moieties. The plant pathogenic fungus V. dahliae has been confirmed to cause serious chlorosis of cultivated S. miltiorrhiza Bunge in China. This study opens the door for further investigation of mutualistic relationships between S. miltiorrhiza Bunge and their endophytic actinomycetes and for possible antifungal agent development for biological control of V. dahliae in the future.