Anticancer natural products from Aspergillus neoniger, an endophyte of Ficus carica

Abstract

Background Several plants have not been investigated for their endophytes, such as the medicinal plant Ficus carica for which anticancer activity has been confirmed. The endophyte Aspergillus neoniger was selected for investigation of its metabolites since it exerted anticancer activities in preliminary screening assays. Results Bioactivity-guided chromatographic fractionation was performed on the endophytic extract and resulted in the identification of asperazine and asperazine A through spectroscopic analysis. Moderate cytotoxicity against HeLa cell lines (CC50 = 18.4 µg mL−1) and moderate antiproliferative effects against HUVEC and K-562 cell lines (GI50 = 31.5 and 24.8 µg mL−1, respectively) were observed for asperazine. Asperazine A on the other hand showed weak cytotoxic activity against HeLa cell lines (CC50 = 34.6 µg mL−1) as well as weak cytostatic activities against HUVEC and K-562 cell lines (GI50 = 40.7 and 50.2 µg mL−1, respectively) while no antimicrobial activity was detected for both compounds. Conclusions These results suggest contribution of A. neoniger to the reported anticancer activity of the host plant and provides a new source of anticancer metabolites with therapeutic potential.

Endophytic Fungi and Secondary Metabolites of Rehmannia Glutinosa Based on Traditional Chinese Medicine Fingerprints

“…Zhu et al extracted a new compound from the endophytic fungus of Safflower, and verified its bioprotective activity [ 4 ]. Abdou et al studied the anticancer activity of the endophytic fungus Aspergillus sinigera in figs [ 5 ]. Although there are many studies on endophytes and their secondary metabolites, there are only a few studies on the endophytes of Rehmannia glutinosa.…”

In Vitro Phytobiological Investigation of Bioactive Secondary Metabolites from the Malus domestica-Derived Endophytic Fungus Aspergillus tubingensis Strain AN103

“…Our cytotoxicity assay showed moderate cytotoxicity of asperazine against the mouse lymphoma cell line L5178Y, while other pure compounds were reported to have weak cytotoxicity. Asperazine was isolated previously from A. tubingensis and was found to exert cytotoxic activity against leukemia cells but did not show reasonable antimicrobial activities [47]. The chemical analysis of extracts of 177 A. tubingensis strains, 140 A. niger strains, 47 A. acidus strains, and 1 A. vadensis strain reported production of asperazine only by A. tubingensis and A. acidus, which indicates the biosynthesis of asperazine can be considered a differential marker to distinguish multiple toxic black aspergilli from other low-toxicity strains, such as A. tubingensis and A. acidus [48].…”

Chemical synthesis in competition with global genome mining and heterologous expression for the preparation of dimeric tryptophan-derived 2,5-dioxopiperazines

“…87 Moderate activities of (+)-asperazine ( 18) against the human immortal cancer cell line (HeLa) and moderate cytostatic activity against human umbilical vein endothelial cells (HUVEC) and human immortalized myelogeneous leukemia cells (K-562), namely 19.2, 31.4 and 24.6 mg mL À1 (CC 50 values), respectively, were more recently reported. 86 No antimicrobial activity was detected upon using the conducted agar diffusion assay. 86 (+)-Asperazine B ( 19) and (+)-asperazine C (20, Fig.…”

“…86 No antimicrobial activity was detected upon using the conducted agar diffusion assay. 86 (+)-Asperazine B ( 19) and (+)-asperazine C (20, Fig. 4) were more recently isolated from Aspergillus tubigensis OUCMBIII 143291 following studies aimed to discover diagnostic chemical markers for identication of black aspergilli species different than Aspergillus niger.…”

“…87 Moderate activities of (+)-asperazine A (25) against the human immortal cancer cell line (HeLa) (CC 50 value of 34.4 mg mL À1 ) and weak cytostatic activities against human umbilical vein endothelial cells (HUVEC) and human immortalized myelogenous leukemia cells (K-562), but no antimicrobial activity in the conducted agar diffusion assay were found for the natural product. 86 (+)-Pestalazine B (26, Fig. 5) was another of the heterodimeric dioxopiperazine alkaloids (together with (+)-pestalazine A 21, Fig.…”