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Novel toxins produced by the dinoflagellate Karenia brevisulcata

机译:鞭毛小鞭毛藻产生的新型毒素

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Karenia brevisulcata (Chang), a new toxic dinoflagellate of the genus Karenia was isolated from a harmful algal bloom that occurred in Wellington Harbour, New Zealand in 1998. The bloom severely affected most marine biota resulting in long-term ecological damage and causing respiratory distress in harbour bystanders. Cultures of K. brevisulcata produced a range of novel toxins including ten lipid-soluble K brevisulcata toxins (KBTs) and six water-soluble brevisulcatic acids (BSXs). Brevetoxins were not detected. KBT-F, KBT-G, BSX-1 and BSX-2 were isolated from 1450 L of bulk cultures and purified in mg quantities. Preliminary chemical and toxicological investigations show that KBT-F (M 2054 C_(107)H_(160)O_(38)) and KBT-G (M 2084 C_(108)H_(162)O_(39)) are complex polycyclic ethers with UVmax at 227 nm. NMR data gave characteristics of ladder frame polyether structures and a 2-methylbut-2-enal side chain, similar to gymnocins. The mouse i.p. LD_(50)s for KBT-F and -G were 0.032 and 0.040 mg kg"1, respectively. These KBTs were also highly cytotoxic and haemolytic. BSX-1 (M 916 C_(49)H_(72)O_(16)) and BSX-2 (M 872 C_(47)H_(68)O_(15)) are polycyclic ether dicarboxylates with UVmax 196 nm. BSX-4 and BSX-5, the lactone ring-closed analogues and the presumed primary toxins in the algal cells, were isolated in smaller quantities. Preliminary structural information from NMR and MS showed a carboxylated side chain and some similarities to brevetoxin-A. However, the structures have not yet been fully elucidated due to conformers confounding the NMR. The mouse i.p. LD_(50) for BSX-1 was 3.9 mg kg~(-1) while no deaths were seen in mice injected with BSX-2 at 6.6 mg kg~(-1). The LD_(50)s for the lactones BSX-4 and -5 were 1.4 and 1.6 mg kg~(-1) respectively. BSX-4 and -5 were agonists of voltage-gated sodium channels but only weakly haemolytic. Activities in the Neuro-2a cytotoxicity assay were ca 10% of dihydrobrevetoxin-2 and were fully antagonised by saxitoxin.
机译:从1998年在新西兰惠灵顿港发生的有害藻华中分离出一种新的有毒的卡伦尼亚有毒鞭毛藻(Karenia brevisulcata,Chang)。该藻华严重影响了大多数海洋生物群,造成长期生态破坏,并导致呼吸窘迫。在港口旁观者。短杆菌K.的培养物产生了一系列新颖的毒素,包括十种脂溶性短杆菌K毒素(KBT)和六种水溶性短囊酸(BSX)。未检测到布雷维毒素。从1450 L的大量培养物中分离KBT-F,KBT-G,BSX-1和BSX-2,并以mg量纯化。初步化学和毒理学研究表明KBT-F(M 2054 C_(107)H_(160)O_(38))和KBT-G(M 2084 C_(108)H_(162)O_(39))是复杂的多环醚UVmax在227 nm下。 NMR数据显示了梯形框架聚醚结构和2-甲基丁-2-烯侧链的特征,类似于裸子霉素。鼠标i.p. KBT-F和-G的LD_(50)s分别为0.032和0.040 mg kg“ 1。这些KBT也具有高度的细胞毒性和溶血性。BSX-1(M 916 C_(49)H_(72)O_(16) )和BSX-2(M 872 C_(47)H_(68)O_(15))是UVmax 196 nm的多环醚二羧酸盐.BSX-4和BSX-5,内酯环封闭的类似物以及假定的初级毒素来自NMR和MS的初步结构信息显示羧化的侧链以及与短毒素A的相似之处,但由于构象异构体使NMR混乱,因此尚未完全阐明其结构。 BSX-1的LD_(50)为3.9 mg kg〜(-1),而注射6.6 mg kg〜(-1)的BSX-2的小鼠未见死亡。 4和-5分别为1.4和1.6 mg kg〜(-1); BSX-4和-5是电压门控钠通道的激动剂,但仅具有弱溶血作用;在Neuro-2a细胞毒性试验中,活性约为10%的二氢brevetoxin -2和分别是被毒素毒素拮抗的花粉。

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