Structure Elucidation of Two Intriguing Neo-Debromoaplysiatoxin Derivatives from Marine Cyanobacterium <i>Lyngbya</i> sp. Showing Strong Inhibition of Kv1.5 Potassium Channel and Differential Cytotoxicity
Zijun Chen,
Na Chen,
Peng Fu,
Weiping Wang,
Shilin Bian,
Huihui Zhang,
Sicheng Shen,
Bingnan Han
Affiliations
Zijun Chen
Department of Development Technology of Marine Resources, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
Na Chen
Department of Development Technology of Marine Resources, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
Peng Fu
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Weiping Wang
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Shilin Bian
Department of Development Technology of Marine Resources, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
Huihui Zhang
Department of Development Technology of Marine Resources, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
Sicheng Shen
Department of Development Technology of Marine Resources, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
Bingnan Han
Department of Development Technology of Marine Resources, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
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.
