Bioactive endophytic fungi isolated from Caesalpinia echinata Lam. (Brazilwood) and identification of beauvericin as a trypanocidal metabolite from Fusarium sp.

Aiming to identify new sources of bioactive secondary metabolites, we isolated 82endophytic fungi from stems and barks of the native Brazilian tree Caesalpiniaechinata Lam. (Fabaceae). We tested their ethyl acetate extracts in several in vitroassays. The organic extracts from three isolates showed antibacterial activityagainst Staphylococcus aureus and Escherichia coli [minimal inhibitory concentration(MIC) 32-64 μg/mL]. One isolate inhibited the growth of Salmonella typhimurium (MIC64 μg/mL) and two isolates inhibited the growth of Klebsiella oxytoca (MIC 64 μg/mL),Candida albicans and Candida tropicalis (MIC 64-128 μg/mL). Fourteen extracts at aconcentration of 20 μg/mL showed antitumour activities against human breast cancerand human renal cancer cells, while two isolates showed anti-tumour activitiesagainst human melanoma cancer cells. Six extracts were able to reduce theproliferation of human peripheral blood mononuclear cells, indicating some degree ofselective toxicity. Four isolates were able to inhibit Leishmania (Leishmania)amazonensis and one isolate inhibited Trypanosoma cruzi by at least 40% at 20 μg/mL.The trypanocidal extract obtained from Fusarium sp. [{"type":"entrez-nucleotide","attrs":{"text":"KF611679","term_id":"560187972","term_text":"KF611679"}}KF611679] culture was subjectedto bioguided fractionation, which revealed beauvericin as the compound responsiblefor the observed toxicity of Fusarium sp. to T. cruzi. This depsipeptide showed ahalf maximal inhibitory concentration of 1.9 μg/mL (2.43 μM) in a T. cruzi cellularculture assay.