Griseofulvin, Diketopiperazines and Cytochalasins from Endophytic Fungi Colletotrichum crassipes and Xylaria sp., and Their Antifungal, Antioxidant and Anticholinesterase Activities

Vanessa Chapla,Mariana Cafeu,Vanderlan Bolzani,Maria Young,Alberto Cavalheiro,Geraldo Silva,Angela Araujo,Ludwig Pfenning,Maria Zeraik

doi:10.21577/0103-5053.20180045

Abstract

One new natural product, 1-phenylethyl-O-a-L-rhamnopyranoside, together with eight known diketopiperazines and two benzene derivatives were isolated from the endophytic fungus Colletotrichum crassipes, whereas six known compounds including two griseofulvins, three cytochalasins and one dihydroisocoumarin were produced from the endophyte Xylaria sp., both endophytic fungi are associated with leaves of Casearia sylvestris. Cyclo(D)-Pro-(D)-Phe, N-(2-phenylethyl)acetamide and 5-carboxy-6-hydroxy-3-methyl-3,4-dihydroisocoumarin exhibited potent antifungal activity against Cladosporium cladosporioides and C. sphaerospermum. The compounds cyclo(D)-Pro-(D)-Phe, griseofulvin, cytochalasin B and cytochalasin D exhibited antioxidant activity, and the compounds cyclo(D)-Pro-(D)-Phe, cytochalasin B and cytochalasin C showed potent acetylcholinesterase (AChE) inhibition. In addition, this is the first report on the isolation of secondary metabolites from two endophytic fungal strains, associated with Casearia sylvestris.

Highlights

Casearia genus (Salicaceae) is found in tropical and subtropical regions
The chemical investigation of the C. crassipes and Xylaria sp., which were isolated from the leaves of C. sylvestris, yielded seventeen compounds
The molecular structures of all isolated metabolites were elucidated based on the interpretation of their 1D- and 2D-nuclear magnetic resonance (NMR) spectra and high-resolution mass spectrometry (HRMS) analysis, which were compared with standards or previously reported literature data

Summary

Introduction

Casearia genus (Salicaceae) is found in tropical and subtropical regions. We report the isolation, structural elucidation, and biological activities (antioxidant, antifungal and acetylcholinesterase inhibition) of the new compound 1-phenylethyl-O-α-L-rhamnopyranoside (1) isolated from C. crassipes, together with eight known diketopiperazines 2-9, N-(2-phenylethyl) acetamide (10) and tyrosol (11), which are secondary metabolites isolated for the first time from this endophyte (Figure 1). The crude EtOAc extract A (380.0 mg) from C. crassipes, which was obtained from large-scale culture, it was fractionated by CC over C18 silica gel (Merck) as the stationary phase and eluted with an H2O-CH3OH gradient (95:05 → 0:100) and CH3OH-EtOAc (50:50 → 0:100), to yield fourteen fractions (AFr1-AFr14).

Results

Conclusion