Discovery of Bergamotanes against Hepatic Ischemia–Reperfusion Injury Based on DeepSAT Technology from Paraconiothyrium sp. H–B

Hepatic ischemia–reperfusion injury (HIRI) is
a common and
inevitable complication of liver surgery that induces severe hepatic
functional impairment and can trigger multiple organ dysfunction syndrome.
From the rice culture of Paraconiothyrium sp. H–B collected from Hypericum wilsonii N. Robson, 11 novel bergamotane-type sesquiterpenoids, paramotanes
A-K (1–11), along with three known
congeners, were obtained by the guidance of the DeepSAT system (a
neural network-based tool for HSQC spectrum analysis). The structures
and configurations of these compounds were confirmed via spectroscopic analysis, single-crystal X-ray diffraction, and electronic
circular dichroism (ECD) calculations. Notably, compound 1 is the first reported 10-nor-bergamotane sesquiterpenoid.
The pharmacodynamics assays demonstrated that compound 12 exhibits hepatoprotective effects and can ameliorate liver function
in HIRI mice, positioning it as a promising leading compound for developing
novel hepatoprotective agents for the clinical management of HIRI.