Bioactive Alkaloids from Endophytic Aspergillus fumigatus

Abstract

Two new alkaloids, named 9-deacetylfumigaclavine C (1) and 9-deacetoxyfumigaclavine C (2), along with 12 known compounds (3-14), were isolated from the culture of Aspergillus fumigatus. The structures of the new compounds were elucidated by comprehensive spectroscopic analyses. Compound 2 showed selectively potent cytotoxicity against human leukemia cells (K562) with an IC(50) value of 3.1 microM, which was comparable to that of doxorubicin hydrochloride, a presently prescribed drug for the treatment of leukemia. Furthermore, 14-norpseurotin (4) significantly induced neurite outgrowth of rat pheochromocytoma cells (PC12) at a 10.0 microM concentration.

Heterologous Expression of Lysergic Acid and Novel Ergot Alkaloids in Aspergillus fumigatus

“…An unexpected and important finding of this study was the accumulation of two novel alkaloids, unknowns A and B, from both transformants but in greater quantities in the easA-easH transformants, which accumulated greater concentrations of (36,37). Genetic evidence of prenylation is presented in Table 3.…”

“…(iv) The fluorescence properties of each analyte and their long retention times in reverse-phase HPLC are consistent with predicted properties of prenylated forms of agroclavine and setoclavine. (v) The recent discovery of reverse-prenylated versions of festuclavine and fumigaclavine B in A. fumigatus (37) indicates that EasL (FgaPT1) accepts other ergot alkaloids as the substrates. While our precursor-feeding and LC/MS data strongly indicate that EasL (FgaPT1) prenylates agroclavine and setoclavine, our proposal that the prenyl group is attached at position 2 in reverse mode can only be hypothesized on the basis of previous mechanistic studies of this enzyme (36) and the consistency of this mode and position of prenylation with other ergot alkaloids of A. fumigatus (36,37).…”

“…(v) The recent discovery of reverse-prenylated versions of festuclavine and fumigaclavine B in A. fumigatus (37) indicates that EasL (FgaPT1) accepts other ergot alkaloids as the substrates. While our precursor-feeding and LC/MS data strongly indicate that EasL (FgaPT1) prenylates agroclavine and setoclavine, our proposal that the prenyl group is attached at position 2 in reverse mode can only be hypothesized on the basis of previous mechanistic studies of this enzyme (36) and the consistency of this mode and position of prenylation with other ergot alkaloids of A. fumigatus (36,37). Interestingly, we saw no evidence of prenylation of lysergic acid in easA-cloA-expressing A. fumigatus, indicating that the carboxylic acid at carbon 17 interfered with enzyme binding or activity.…”

Fungal Endophytes: An Amazing and Hidden Source of Cytotoxic Compounds

“…It exhibited potent cytotoxicity against human leukemia cells (K562) with an IC 50 value of 3.1 µM, while doxorubicin hydrochloride, a drug which is currently used for the treatment of leukemia at 1.2 µM (Ge et al 2009). …”

Characterization, Synthesis and Self‐Aggregation of (−)‐Alternarlactam: A New Fungal Cytotoxin with Cyclopentenone and Isoquinolinone Scaffolds

“…The experiment was performed in triplicate, and the data expressed as means AE SD. [32] ECD calculations: Density functional theory (DFT) at B3LYP/6-31 + G-A C H T U N G T R E N N U N G (d,p) level was employed to optimize the geometry of (À)-1 and (+)-1. Subsequently, the corresponding TDDFT calculations with the same basis set were performed on the basis of the ground-state optimized structures.…”