Structure Elucidation of Two Intriguing Neo-Debromoaplysiatoxin Derivatives from Marine Cyanobacterium Lyngbya sp. Showing Strong Inhibition of Kv1.5 Potassium Channel and Differential Cytotoxicity

Abstract

Two aplysiatoxin derivatives, neo-debromoaplysiatoxin I (1) and neo-debromoaplysiatoxin J (2), were isolated from marine cyanobacterium Lyngbya sp. collected from the South China Sea. Their structures including absolute configurations were assigned by spectroscopic analysis, in combination with GIAO NMR shift calculation and DP4+ analysis. Structures of neo-debromoaplysiatoxin I and neo-debromoaplysiatoxin J contained a decahydro-5H-pyrano [2,3,4-de] chromen-5-one 6/6/6 ring skeleton and an intriguing peroxide bridge group, respectively, which are unprecedented structure scaffold and motif in aplysiatoxins. Two compounds displayed comparable inhibitory activities against Kv1.5 K+ channel with IC50 values of 2.59 ± 0.37 μM (1) and 1.64 ± 0.15 μM (2); however, they presented differential cytotoxic effects. It is worth noting that neo-debromoaplysiatoxin J, containing a peroxide bridge, showed remarkable cytotoxicity against four cancer cell lines including SW480, SGC7901, LoVo and PC-9 compared to the human normal cell line.

Determination of the Absolute Configuration of Secondary Alcohols in a Compound Mixture via the Application of Competing Enantioselective Acylation Coupled with LC/MS Analysis

“…This process entailed the experimental NMR data comparison with the calculated Gauge-Independent Atomic Orbital (GIAO) NMR chemical shifts and δ x calc values for potential isomers. The DP4+ analysis was executed utilizing an Excel sheet [ 30 , 31 , 32 , 33 ].…”

Recent Reports on Bioactive Compounds from Marine Cyanobacteria in Relation to Human Health Applications

“…The cytotoxicity of these compounds was assessed using the SW480 human colorectal carcinoma cell line, SGC7901 human gastric cancer cells, LoVo human colorectal carcinoma cells, and PC-9 non-small-cell lung cancer cells. According to the obtained data, neo-debromoaplysiatoxin I resulted in weak cytotoxic activity while neo-debromoaplysiatoxin J exhibited strong cytotoxic activity against the tested cancer cell lines, with less than 20% cell viability [ 42 ]. The marine cyanobacterium Lyngbya sp.…”

Hot off the Press

“…Neodebromoaplysiatoxin J 14 , featuring an unusual peroxy bridge, is produced by a Lyngbya species collected from the South China Sea. 12 The authors propose a biosynthetic pathway for the formation of neodebromoaplysiatoxin J 14 .…”