Abstract
Seven previously unreported sesquiterpenes including three rare 5/5/6-fused tricyclic gymnomitrane-type sesquiterpenes (1-3), an ent-longipinane-type sesquiterpene (4), a cuparane-type sesquiterpene (5), and two chamigrane-type sesquiterpenes (6 and 7), along with a known chamigrane-type sesquiterpene xylariterpenoid C (8) were isolated from the hydrothermal vent sediment derived fungus Penicillium sp. JWM79-5-1. Their structures were identified on the basis of 1D and 2D NMR, in conjunction with Mosher's method, X-ray crystallography, and electronic circular dichroism (ECD). The antithrombotic activity of compounds 1-6 and 8 was evaluated in arachidonic acid (AA)-induced zebrafish thrombosis model in vivo. The results revealed compound 1 with potent antithrombotic activity in a concentration-dependent manner. Further, the pro-angiogenic activities of compounds 1-6 and 8 were evaluated in a transgenic zebrafish model that expresses vegfr2, the receptor for the angiogenic factor VEGF, tagged with the green fluorescence protein (vegfr2-GFP) through detecting the length of both intersegmental vessels (ISVs) and subintestinal veins (SIVs). The results revealed that compound 1 exhibited a potent antithrombotic activity while 3 revealed a potent pro-angiogenic activity. These findings strongly support drug development of these compounds in cardiovascular disease treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-025-00303-y.