Cytotoxic Metabolites of Alternaria Alternata, an Endophyte of the Medicinal Plant Bidens Bipinnata

Abstract

Objective: Endophytes are widely spread in the plant kingdom and represent a very promising source of biologically active natural products. The medicinal plant Bidens bipinnata Lin. (Asteraceae) which is known for its anti-inflammatory, antifungal and antitumor effects has been chosen for the investigation of its endophyte to search for bioactive metabolites.
 Methods: An endophytic Alternaria alternata species was isolated from the leaves of the plant B. bipinnata Lin. To investigate the metabolic profile of this endophytic fungus it was cultivated in several culture media as static and shaken culture. The antimicrobial and cytotoxic activities of the ethyl acetate extracts of the fungus were examined. Extracts exhibiting highest antimicrobial activities in agar diffusion assay and cytotoxicity against HeLa cancer cell line were subjected to activity-guided chromatographic fractionation for the identification of bioactive metabolites. A cytotoxic assay was performed on the isolated compounds against HeLa cancer cell lines as well as cytostatic activity tests against HUVEC and K-562 cell lines.
 Results: Chromatographic fractionation resulted in the isolation and identification of alternariol and tentoxin from the extract of the fungus cultivated in medium M5 while sterigmatocystin was isolated in addition to alternariol and tentoxin from the extract of the fungus grown in medium M25. Both alternariol and sterigmatocystin proved to be of moderate cytotoxicity and weak cytostatic activity with alternariol showing higher cytotoxic activity than sterigmatocystin. Highest cytotoxicity against HeLa cell lines was observed for tentoxin with a CC50 of 22.5 µg/ml.
 Conclusion: This study presents the isolation and identification of the bioactive metabolites alternariol, sterigmatocystin and tentoxin from the endophyte A. alternata in addition to the antifungal activity of the strain extract as well as the cytotoxic and cytostatic activities of the isolated metabolites against HeLa, HUVEC and K-562 cell lines, respectively.

Entomotoxic Activity of the Extracts from the Fungus, Alternaria tenuissima and Its Major Metabolite, Tenuazonic Acid

“…However, the entomotoxic activity of the compounds is unknown, while their cytotoxic activity has not been sufficiently studied. For instance, weak cytotoxicity of tentoxin against HepG2 [38] and HeLa cell lines [39] as well as some TCAs for various tumor cell lines [40,41] have been reported. A relationship between the production of TCAs and the cytotoxic activity of A. tenuissima MFP253011 extracts against Sf9 cells is more likely (Figure 7).…”

Entomotoxic Activity of the Extracts from the Fungus, <em>Alternaria tenuissima</em> and Its Major Metabolite, Tenuazonic Acid

“…However, entomotoxic activity of the compounds is unknown while their cytotoxic activity has not been sufficiently studied. For instance, weak cytotoxicity of tentoxin against HepG2 [38] and HeLa cell lines [39] as well as some TCAs for various tumor cell lines [40,41] was reported. Relation between the production of TCAs and cytotoxic activity of A. tenuissima MFP253011 extracts against Sf9 cells is more likely (Figure 7).…”