Discovery of Quebrachamine-like Indole Alkaloids with Ferroptosis Inhibitory Activity from Catharanthus roseus Using HSQC-Based DeepSAT

Velbanamines A-L (1–12), 12 novel quebrachamine-like indole alkaloids, were isolated from Catharanthus roseus L. (G.) Don under the guidance of HSQC-based DeepSAT. Their structures and absolute configurations were elucidated unambiguously by comprehensive spectroscopic analyses, single-crystal X-ray diffraction analysis, and electronic circular dichroism (ECD) calculations and computational calculations. Structurally, compound 1 features a unique skeleton with a 6/5/8/5 tetracyclic system. The plausible biosynthetic pathway of 1 was also proposed. In addition, all compounds demonstrated anti-ferroptotic activity in cardiomyocytes. Among them, Compound 8 was the most potent (IC50 = 0.12 ± 0.01 μM), and also suppressed lipid ROS accumulation and regulated ferroptosis-related proteins.