Banker R, Carmeli S, Werman M, Teltsch B, Porat R, Sukenik A
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Israel.
J Toxicol Environ Health A. 2001 Feb 23;62(4):281-8. doi: 10.1080/009841001459432.
A new natural derivative of the sulfated guanidinium zwitterionic toxin cylindrospermopsin, 7-epi-cylindrospermopsin, was recently isolated from the cyanobacterium Aphanizomenon ovalisporum (Forti). The toxicity of the molecule (LD50 ip 5 d), estimated by mouse bioassay, was 200 microg/kg mouse, a value similar to that of cylindrospermopsin. Treatment of cylindrospermopsin with chlorine solution or chlorine-related oxidants produced two new derivatives. The chemical structure of these products was elucidated by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques and toxicity was determined. In the first derivative, the vinylic proton at position 5 of the pyrimidine ring was substituted by chlorine to yield 5-chlorocylindrospermopsin. The other product is a truncated one, where C-6 of the pyrimidine ring was oxidized to a carboxylic acid. A trivial name, cylindrospermic acid, was given to this compound. Both products showed no toxic effects even at doses 50 times higher than the LD50 of cylindrospermopsin (10 mg/kg mouse ip). Based on these results, the pyrimidine ring is postulated as the molecule component essential for the toxicity of cylindrospermopsin.
一种新的硫酸化胍基两性离子毒素柱孢藻毒素的天然衍生物，7-表柱孢藻毒素，最近从卵形鱼腥藻（Forti）中分离得到。通过小鼠生物测定法估计，该分子的毒性（腹腔注射半数致死量为5天）为200微克/千克小鼠，与柱孢藻毒素的值相似。用氯溶液或与氯相关的氧化剂处理柱孢藻毒素产生了两种新的衍生物。通过核磁共振（NMR）和质谱（MS）技术阐明了这些产物的化学结构并测定了毒性。在第一种衍生物中，嘧啶环5位的乙烯基质子被氯取代，生成5-氯柱孢藻毒素。另一种产物是截短的产物，其中嘧啶环的C-6被氧化成羧酸。给这种化合物起了一个俗名，柱孢藻酸。即使在比柱孢藻毒素的半数致死量（10毫克/千克小鼠腹腔注射）高50倍的剂量下，这两种产物也均未显示出毒性作用。基于这些结果，推测嘧啶环是柱孢藻毒素毒性所必需的分子成分。
