ABSTRACT
Neo-debromoaplysiatoxin C (1), a new member of the aplysiatoxin family, was isolated from the marine cyanobacterium Lyngbya sp. The structure of 1 was elucidated based on spectroscopic data, and its stereochemistry was determined from NOESY spectrum and biosynthetic considerations. This new compound presents an intriguing 10-membered lactone ring skeleton derived from debromoaplysiatoxin by structural rearrangement, which is the first example in the aplysiatoxin family. Its biological properties were evaluated for cytotoxicity, PKCδ activation and inhibitory effects on potassium channel.
Subject(s)
Cyanobacteria/chemistry , Lyngbya Toxins/chemistry , Cytotoxins/pharmacology , Lactones/chemistry , Lactones/pharmacology , Magnetic Resonance Spectroscopy , Molecular Structure , Potassium Channel Blockers/pharmacology , Protein Kinase C-delta/drug effects , Seaweed/chemistryABSTRACT
The isolation and structure elucidation of two cyanobacterial debromoaplysiatoxin (DAT) analogues, neo-debromoaplysiatoxin A (1) and neo-debromoaplysiatoxin B (2), were reported and found to possess 6/10/6 and 6/6/6 fused-ring systems, respectively, which are rarely seen among aplysiatoxins. Both compounds exhibited potent blocking activity against Kv1.5 with IC50 values of 6.94 ± 0.26 and 0.30 ± 0.05 µM, respectively. These findings suggest the potential of aplysiatoxin analogues in modulating ionic channels and also provide links between the DAT target, protein kinase C, and cell regulation.
