Antibacterial harziane diterpenoids from a fungal symbiont Trichoderma atroviride isolated from Colquhounia coccinea var. mollis

Fungal endophytes from plants are an important source for discovery of novel bioactive natural products. In this study, five undescribed harziane diterpenoids with a 4/7/5/6 tetracyclic scaffold, harzianols F-J and three known derivatives, were obtained from the liquid fermentation of an endophytic fungus Trichoderma atroviride B7, which was isolated from the healthy flower of a Lamiaceae plant Colquhounia coccinea var. mollis. Their structures were elucidated by comprehensive spectroscopic analyses and X-ray crystallographic diffraction in the case of harzianol F. Harzianol I exhibited significant antibacterial effect against the growth of Staphylococcus aureus (EC50 = 7.7 +/- 0.8 mu g/mL), Bacillus subtilis (EC50 = 7.7 +/- 1.0 mu g/mL), and Micrococcus luteus (EC50 = 9.9 +/- 1.5 mu g/mL). Meanwhile, cytotoxic activity of harzianol I against three cancer cell lines was also observed. A plausible biosynthetic pathway for harziane diterpenoids was proposed.