Studies On Chemical Constituents And Biological Activities Of Aplysiatoxins From The Marine Cyanobacterium Lyngbya Sp. In The South China Sea

The particularity of marine environment results in the diversity of chemical structures and biological activities of secondary metabolites of marine cyanobacteria.In order to uncover more natural products with novel structure and specific biological activity from marine cyanobacteria,the cyanobacterium Lyngbya sp.,collected from Zaozai Village,South China Sea,was studied on chemical constituents and investigated on biological activity.Three new compounds,neo-debromoaplysiatoxin D?4?and oscillatoxins E-F?6-7?,along with four known compounds,anhydrodebromoaplysiatoxin?1?,debromoaplysiatoxin?2?,3-methoxydebromoaplysiatoxin?3?and 30-methyloscillatoxin D?5?,were isolated and characterized from the cyanobacterium,Lyngbya sp.The metabolites'structures were determined based on a combination of 1D-NMR,2D-NMR,HRESIMS,optical rotation comparison,ECD comparison,biosynthesis pathway and auxiliary reference comparison.Bioactivity experiments showed that compounds 1-4 presented significant expression of phosphor-PKC?whereas compounds 2,5,6 and 7 showed the most potent blocking activity against voltage-gated potassium channel Kv1.5 with IC₅₀0 values of 1.28�0.080?M,1.47�0.138?M,0.79�0.032?M and 2.03�0.45?M,respectively.The mechanism of interaction between compounds 1-7 and Kv1.2was studied by molecular docking technology,and compared with the known Kv1.2inhibitors.The results showed that ATXs has a good binding ability with Kv1.2.Among them,the binding energy of compounds 2-4 and 6 with Kv1.2 is stronger than that of the known Kv1.2 inhibitor,indicating that ATXs were potential Kv1.2inhibitors which worth studying.