Tagpyrrollins A and B and Tagpyrrollidone A: Three Pyrrole Steroid Analogues with AKR1B1-Targeting Inhibitory Activity from the Sponges Stylissa massa and Pseudospongosorites suberitoides .

Pyrrole alkaloids (PAs) are a diverse class of natural products with complex carbon frameworks and broad bioactivities that are usually derived from marine sponges. Stylissa massa and Pseudospongosorites suberitoides are two independent sponges collected from the South China Sea in 2013 and 2018, respectively. We discovered PAs are common constituents in both two sponges; more specifically, S. massa produces pyrrole-imidazole alkaloids, and P. suberitoides contains pyrrolidone alkaloids. In this study, three pyrrole steroid metabolites were obtained. Compounds 1 and 2 are a pair of epimers sharing a new 5/7/5/6/6 pentacyclic structural configuration, and compound 3 has a new rigid 5/6/6 tricyclic structure. Interestingly, their scaffolds all possess a 6/6 bicyclic system on the featured classic pyrrole/pyrrolidone skeletons, so-dubbed tagpyrrollins A and B ( 1 and 2 , respectively) and tagpyrrollidone A ( 3 ). From a biosynthetic viewpoint, 4,5-dihydroxypent-2-enal probably plays a crucial role in constructing these pyrrole steroid analogues. Based on our previous study on the inhibitory activity of spongiacidin targeting AKR1B1, a drug target for the treatment of chronic diabetic complications, in this study we found that tagpyrrolin A ( 1 ) also exhibits an inhibitory effect against AKR1B1.