Absolute Configuration of New Cytotoxic and Other Bioactive Trichothecene Macrolides

Abstract

Three new cytotoxic 10,13-cyclotrichothecane-derived macrolides, myrothecines A-C (1-3), were characterized from the extracts of two Myrothecium roridum strains, IFB-E009 and IFB-E012, isolated as endophytic fungi found on the traditional Chinese medicinal plants Trachelospermum jasminoides and Artemisia annua, respectively. The absolute configuration of myrothecines A-C was elucidated by a combination of spectral techniques (UV, IR, MS, circular dichroism (CD), (1)H and (13)C NMR, DEPT, (1)H-(1)H COSY, NOESY, HMQC, and HMBC spectrascopic analyses), Mosher's ester analysis, and single-crystal X-ray diffraction. The absolute configuration of the reported bioactive analogue, mytoxin B was established by correlating its spectral data with that of known absolute configurational structures. Furthermore, the significance in endophytism (or symbiosis) and biocatabolism, highlighted by production of those macrolides by the endophytic strains, is discussed in brief.

Endophytic fungi from Nerium oleander L (Apocynaceae): main constituents and antioxidant activity

“…Rodrigues et al (2005) reported the extracts from endophytic fungi of some Apocynaceae plants showed a high cholinesterase inhibitory activity. In addition, some novel cytotoxic trichothecene macrolides and anticancer compounds were found in the endophytic fungi isolated from Trachelospermum jasminoides (Apocynaceae) (Shen et al 2006;Zhang et al 2005). Antioxidants are thought to be highly profitable in the management of reactive oxygen species-mediated tissue impairments.…”

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

“…[7,9,10] Strain and cultivation: The alternarlactam-producing fungus, identified by Dr. Y. C. Song as Alternaria sp. HG1 according to its macro-and micro-graphic morphological characteristics, [27] was isolated from inside the fresh Carex aridula leaves collected in November 2001 from the suburb of Nanjing, China.…”

“…[4][5] This observation fundamentalizes that endophytes, as a big special group of microorganisms, are a rich source of functional biomolecules as substantiated by our characterization of new symbiont metabolites with antitumor, [6][7][8] antimicrobial, [9] and immunosuppressive activities. [10] In continuation of our bioassay for the antitumor secondary metabolites from symbiont cultures, the pronounced cytotoxicity against the test cancer cell line was discerned with the extract derived from the culture of Alternaria sp.…”

Symbionts, a promising source of bioactive natural products

“…Eight lactones (105-112, Scheme 7) were isolated from the endophytic fungus Phomopsis species CMU-LMA, and metabolite 106 exhibits a remarkable cytotoxicity against the colonic epithelial cancer cell line HCT-116 cells with an IC 50 value of 41 nmol/L [34]. Four cytotoxic macrolides including three new (113-115, Scheme 7) and roridin E (116, Scheme 7) were isolated from two Myrothecium roridum strains IFB-E009 and IFB-E012 [35]. Compound 116 was further re-isolated from another endophytic Myrothecium roridum QDFE005, together with a new cytotoxic macrolide 12′-episatratoxin H (117, Scheme 7) [36].…”