Abstract
A pair of stereoisomers possessing novel structures with 6/6/5 fused-ring systems, neo-debromoaplysiatoxin E (1) and neo-debromoaplysiatoxin F (2), were isolated from the marine cyanobacterium Lyngbya sp. Their structures were elucidated using various spectroscopic techniques including high resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR). The absolute stereochemistry was determined by calculated electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR shift calculation followed by DP4+ analysis. Significantly, this is the first report on aplysiatoxin derivatives with different absolute configurations at C9–C12 (1: 9S, 10R, 11S, 12S; 2: 9R, 10S, 11R, 12R). Compounds 1 and 2 exhibited potent blocking activities against Kv1.5 with IC50 values of 1.22 ± 0.22 μM and 2.85 ± 0.29 μM, respectively.
Highlights
Aplysiatoxins (ATXs) are a class of biologically active dermatotoxins with anti-proliferative activity, tumor-promoting properties, pro-inflammatory actions, antileukemia activity, and antiviral activity [1,2,3,4,5,6]
Using the Merck molecular force field (MMFF) in the Spartan 10 to search for conformations, the conformers with Boltzmann-population of over 5% were chosen to be optimized at the B3LYP/6-31 + g (d, p) level by the conductor polarizable continuum model (CPCM) (MeOH as the solvent)
A pair of stereoisomers, neo-debromoaplysiatoxin E (1) and F (2), were isolated from the marine cyanobacterium Lyngbya sp. This is the first report on aplysiatoxin derivatives with different absolute configurations at C9–C12 (1: 9S, 10R, 11S, 12S; 2: 9R, 10S, 11R, 12R) exhibiting potent potassium channel Kv1.5 blocking activities (IC50 = 1.22 ± 0.22 μM and 2.85 ± 0.29 μM, respectively)
Summary
Aplysiatoxins (ATXs) are a class of biologically active dermatotoxins with anti-proliferative activity, tumor-promoting properties, pro-inflammatory actions, antileukemia activity, and antiviral activity [1,2,3,4,5,6] It was first discovered in the digestive gland of the Stylocheilus longicauda [7,8]. A series of ATX derivatives with Kv1.5 ion channel inhibitory activities have been discovered during our previous studies [10,11,12]. Mar. Drugs 2019, 17, 652 acacetin is considered to be one of the few natural products with selective Kv1.5 ion channel inhibitory activity [26,27]. 1), a pair of stereoisomers with a new ABC ring system (6/6/5 fused-ring system),1), from the derivatives, neo-debromoaplysiatoxin. Lyngbya species activities of[10]
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