Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae)

Abstract

Protozoan parasites belonging to genera Leishmania and Trypanosoma are the etiological agents of severe neglected tropical diseases (NTDs) that cause enormous social and economic impact in many countries of tropical and sub-tropical areas of the world. In our screening program for new drug leads from natural sources, we found that the crude extract of the endophytic fungus Cochliobolus sp. (UFMGCB-555) could kill 90% of the amastigote-like forms of Leishmania amazonensis and inhibit by 100% Ellman's reagent reduction in the trypanothione reductase (TryR) assay, when tested at 20 µg mL−1. UFMGCB-555 was isolated from the plant Piptadenia adiantoides J.F. Macbr (Fabaceae) and identified based on the sequence of the internally transcribed spacer (ITS) regions of its ribosomal DNA. The chromatographic fractionation of the extract was guided by the TryR assay and resulted in the isolation of cochlioquinone A and isocochlioquinone A. Both compounds were active in the assay with L. amazonensis, disclosing EC50 values (effective concentrations required to kill 50% of the parasite) of 1.7 µM (95% confidence interval = 1.6 to 1.9 µM) and 4.1 µM (95% confidence interval = 3.6 to 4.7 µM), respectively. These compounds were not active against three human cancer cell lines (MCF-7, TK-10, and UACC-62), indicating some degree of selectivity towards the parasites. These results suggest that cochlioquinones are attractive lead compounds that deserve further investigation aiming at developing new drugs to treat leishmaniasis. The findings also reinforce the role of endophytic fungi as an important source of compounds with potential to enter the pipeline for drug development against NTDs.

Cochliobolus: an overview and current status of species

“…A crude extract of endophytic Cochliobolus sp. isolated from Piptadenia adiantoides killed 90% of the amastigote-like forms of Leishmania amazonensis, which is a protozoan parasite and are etiological agents of severe neglected tropical diseases (NTDs) (Campos et al 2008). A Bipolaris species was associated with the marine sponge Gelliodes carnosa and showed a close relationship to B. sorokiniana (sexual state: Cochliobolus sativus) (Liu et al 2010), a well known plant pathogen.…”

Microbial Endophytes: Their Resilience for Innovative Treatment Solution to Neglected Tropical Diseases

“…obtained from the plant Piptadenia adiantoides produces cochlioquinone A and isocochlioquinone A. Both compounds were active in an assay against L. amazonensis , with EC 50 values of 1.7 and 4.1 μM, respectively (Campos et al 2008 ). Grandisin, a tetrahydrofuran lignan isolated from Piper solmsianum ( Piperaceae ) (Martins et al 2003 ) and Virola surinamensis ( Myristicaceae ), has potent trypanocidal activity against the trypomastigote form of T. cruzi at 5 μg/mL (Lopes et al 1998 ).…”

Studies on Silver Accumulation and Nanoparticle Synthesis By Cochliobolus lunatus

“…Besides these extracellular enzymes, NADPH as reducing agent [39], several naphthoquinones [40], and anthroquinones [41] having excellent redox properties were reported in F. oxysporum that could act as an electron shuttle in metal reductions [42]. The fungi C. lunatus was also reported for production of chochlioquinones [43].…”