Chemical and Biological Study of Novel Aplysiatoxin Derivatives from the Marine Cyanobacterium <i>Lyngbya</i> sp.

• Main Authors: Hui-Hui Zhang, Xin-Kai Zhang, Ran-Ran Si, Si-Cheng Shen, Ting-Ting Liang, Ting-Ting Fan, Wei Chen, Lian-Hua Xu, Bing-Nan Han
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Toxins
• Subjects: marine cyanobacterium; <i>Lyngbya</i> sp.; aplysiatoxin; Kv1.5 inhibitory activity; brine shrimp toxicity
• Online Access: https://www.mdpi.com/2072-6651/12/11/733

Since 1970s, aplysiatoxins (ATXs), a class of biologically active dermatoxins, were identified from the marine mollusk <i>Stylocheilus longicauda</i>, whilst further research indicated that ATXs were originally metabolized by cyanobacteria. So far, there have been 45 aplysiatoxin derivatives discovered from marine cyanobacteria with various geographies. Recently, we isolated two neo-debromoaplysiatoxins, neo-debromoaplysiatoxin G (<b>1</b>) and neo-debromoaplysiatoxin H (<b>2</b>) from the cyanobacterium <i>Lyngbya</i> sp. collected from the South China Sea. The freeze-dried cyanobacterium was extracted with liquid–liquid extraction of organic solvents, and then was subjected to multiple chromatographies to yield neo-debromoaplysiatoxin G (<b>1</b>) (3.6 mg) and neo-debromoaplysiatoxin H (<b>2</b>) (4.3 mg). They were elucidated with spectroscopic methods. Moreover, the brine shrimp toxicity of the aplysiatoxin derivatives representing differential structural classifications indicated that the debromoaplysiatoxin was the most toxic compound (half inhibitory concentration (IC₅₀) value = 0.34 ± 0.036 µM). While neo-aplysiatoxins (neo-ATXs) did not exhibit apparent brine shrimp toxicity, but showed potent blocking action against potassium channel Kv1.5, likewise, compounds <b>1</b> and <b>2</b> with IC₅₀ values of 1.79 ± 0.22 µM and 1.46 ± 0.14 µM, respectively. Therefore, much of the current knowledge suggests the ATXs with different structure modifications may modulate multiple cellular signaling processes in animal systems leading to the harmful effects on public health.