Mycoleptones A–C and Polyketides from the EndophyteMycoleptodiscus indicus

Abstract

Three new azaphilones with an unusual methylene bridge, named mycoleptones A, B, and C (2, 4, and 5), were isolated from cultures of Mycoleptodiscus indicus, a fungus associated with the South American medicinal plant Borreria verticillata. Additionally, four known polyketides, austdiol (1), eugenitin (3), 6-methoxyeugenin (6), and 9-hydroxyeugenin (7), were also isolated. The structural characterization of compounds was carried out by nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, electronic circular dichroism spectroscopy, time-dependent density functional theory calculations, and X-ray crystallography. Compounds 1-9 were weakly active when tested in antileishmanial and cytotoxicity assays.

Short-Range Solvation Effects on Chiroptical Properties: A Time-Dependent Density Functional Theory and ab Initio Molecular Dynamics Computational Case Study on Austdiol

“…The influence of ring puckering and aldehyde orientation is clearly evident from the theoretical spectra of the conformers of 1: in particular, the ECD spectra of conformers 1.01 and 1.02 (reported in the Supporting Information) are almost opposite, although the absolute stereochemistry of chiral centers is retained.The conformationally-averaged spectra of 1 (Figure 2)show a better correlation with experimental data, mainly in the high-energy spectral region (λ < 300 nm) where the effect of the chiral centers on the π → π* transitions of the conjugated system is stronger; nevertheless, the low-energy spectral region (λ > 300 nm), where the n → π* transitions of carbonyl chromophores are observed, show a lower degree of correlation. Both behaviors are consistent to 12 what previously observed with mycoleptone A15 and are not dependent on the functional and basis set employed in the calculations (see Supporting Information for more details).…”

“…Compound 1 was extracted from cultures of Mycoleptodiscus indicus according to a recently reported procedure 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 30 was employed in all calculations. Input geometries for TD-DFT calculations were generated using the protocols described in the next subsections.…”

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“…Most of the studies on endophytic biodiversity published in Brazil (2012-2017) present some bioprospecting studies, such as evaluation of antibiotic, antioxidant, antiparasitic, or cytotoxicity activities, or the use of endophytes to promote plant growth or reactive dye discoloration [40,[48][49][50][51][52][53][54] (▶ Table 3). As a result of the success obtained in terms of discovering active metabolite-producing endophytes, a large number of compounds [2,[55][56][57] or known compounds with unreported biological properties [33,36,[58][59][60] have been reported.…”

“…Seven new compounds have been reported from endophytes found in Brazil in recent years (▶ Table 3). The compounds belong to four chemical classes, butanolide (γ-lactone, δ-lactone), glyceride (monoacylglycerol) [35], alternariol [2], and azaphilone (mycoleptones) [56] (▶ Table 3). Their chemical structures are listed in ▶ Fig.…”

“…Azaphilones are known for their range of biological activity, such as antimicrobial, nematicidal, and anti-inflammatory [70]. Andrioli et al [56] demonstrated that the new mycoleptones are non-selective compounds with antileishmanial and cytotoxic activities. Secondary metabolites produced by endophytes, in general, are less toxic to eukaryotes than to prokaryotes, since endophytes should not harm the host plant [17].…”