Chemical analysis and anticancer activity of sesterterpenoid from an endophytic fungus Hypomontagnella monticulosa Zg15SU and its host Zingiber griffithii Baker

Zingiber griffithii Baker is one of the native Zingiberaceous species in a tropical forest of North Sumatra, Indonesia. Zingiberaceous species have been intensively studied and reported as herbal ingredients in ethnomedicine and currently their endophytic fungal associates were studied for pharmacological importance. Fifteen endophytic fungi were isolated from Zingiber griffithii following morphological and molecular characterization. All isolates exhibited antibacterial properties to at least one of the tested pathogenic bacteria Staphylococcus aureus, Escherichia coli, Methicilin-resistant S. aureus (MRSA), and Enteropathogenic E. coli (EPEC). The isolate, identified as Hypomontagnella monticulosa strain Zg15SU (syn. Hypoxylon monticulosum Mont.) based on its rDNA/ITS sequence, displayed antibacterial activities to all tested pathogens. The EtOAc extract of the H. monticulosum Zg15SU showed the highest activity for gram-negative bacteria, the E. coli and EPEC, while the extract of Z. griffithii rhizome displayed activity only for E. coli. The gas chromatography-mass spectrometry analysis (GC-MS) indicated a major portion of similar compounds found in both the endophytic fungus and plant extract, revealing the compounds of oleic acid, cyclononasiloxane, octadecamethyl, and eicosanoic acid Furthermore, purification and structural elucidation on the EtOAc extract of both Z. griffithii rhizome and H. monticulosa Zg15SU yielded two bioactive compounds: a novel compound, griffithiiene, a terpenoid-alkaloid bearing the skeleton of a scalarane (1) and scalaradial (2) which were confirmed by (1)H- (500 MHz) and (13)C-NMR (125 MHz) spectroscopy. Importantly, the elucidated compounds showed a cytotoxicity activity against cancer cell lines, the Panc-1, NBT-T2, and HCT116 based on in vitro MTT proliferation assay. This is the first report of Z. griffithii harboring an endophytic fungus, H. monticulosa, which produced potential antibacterial and anticancer metabolites along with its host to be utilized for future prospects.