A Series of New Pyrrole Alkaloids with ALR2 Inhibitory Activities from the Sponge Stylissa massa .

Twelve new and four known alkaloids including five different structural scaffolds were isolated from the sponge Stylissa massa collected in the South China Sea. Compound 1 is the first identified precursor metabolite of the classic 5/7/5 tricyclic skeleton with unesterified guanidine and carboxyl groups, compounds 2 - 5 and 13 - 15 belong to the spongiacidin-type pyrrole imidazole alkaloids (PIAs). Z - and E -configurations of the spongiacidin-type PIAs often appeared concomitantly and were distinguished by the chemical shift analysis of 13 C NMR spectra. The structures of all twelve new compounds were determined by NMR, MS, and ECD analysis combined with single-crystal data of compounds 1 , 5 , and 10 . In the aldose reductase (ALR2) inhibitory assay, six 5/7/5 tricyclic compounds ( 2 - 5 , 13 - 15 ) displayed significant activities. Compounds 13 and 14 , as the representative members of spongiacidin-PIAs, demonstrated their ALR2-targeted activities in SPR experiments with K D values of 12.5 and 6.9 µM, respectively.