PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

天然产物提供了广泛的生物活性剂， 其中许多具有独特的药理活性特征， 治疗潜力 已经有超过四百种生物碱 在两栖动物皮肤的提取物中发现。 这些包括 蛙毒素是钠通道的有效激活剂， 组蛋白毒素，是烟碱类非竞争性阻断剂， 受体通道复合物和钾通道，短小毒素， 其由于对钠的作用而具有肌强直和心强直活性 通道和地棘蛙素，一种非常有效和选择性的烟碱 具有显著抗伤害感受活性的激动剂。 其他生物碱 包括2，5-二取代十氢喹啉、3，5-二取代 吡咯烷，3，5-二取代的吲嗪，5，8-二取代的 吲嗪，1，4-二取代和4，6-二取代喹嗪， 短小毒素-高短小毒素-别短小毒素类，和 各种三环生物碱，包括吡咯里西啶肟， 假菲林胺、环戊喹嗪啶和胭脂碱。 最 这些生物碱已被检测和表征，从 新热带树蛙 Pumiliotoxins也出现在一个属中 澳大利亚肌蛙科的一种，属于南美洲 蟾蜍科的蟾蜍和马达加斯加的一个属的曼氏蛙。 它 似乎所有蛙皮生物碱都有饮食来源， 并保持不变地进入皮肤腺体。 蚂蚁、甲虫和 千足虫似乎是某些蛙皮生物碱的来源。 现在已经在蚂蚁中发现了十氢喹啉。 的起源 蟾毒毒素、组胺毒素、短小毒素和表蛙肽 青蛙皮中发现的蛋白质仍然是个谜 结构已经 测定了1，4-二取代喹嗪啶、三取代喹嗪啶、 吲哚里西啶，一种与胭脂虫碱有关的新的三环生物碱， 二聚十氢喹啉，一组十九碳 来自青蛙和蚂蚁的十氢喹啉和含环氧乙烷的 别普米利欧毒素 螺吡咯里西啶肟类 一系列托烷生物碱（潜在的毒蕈碱/烟碱激动剂） 和强效烟碱的甲基异恶唑类似物（epioxidine） 合成了用于生物学评价的无菌地棘蛙素。

Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over four hundred alkaloids have been identified in extracts from amphibian skins. These include batrachotoxins, which are potent activators of sodium channels, histrionicotoxins, which are noncompetitive blockers of nicotinic receptor channel complexes and potassium channels, pumiliotoxins, which have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, an extremely potent and selective nicotinic agonist with remarkable antinociceptive activity. Further alkaloids include 2,5-disubstituted decahydroquinolines, 3,5-disubstituted pyrrolizidines , 3,5-disubstituted indolizidines, 5,8-disubstituted indolizidines, 1,4-disubstituted and 4,6-disubstituted quinolizidines, the pumiliotoxin-homopumiliotoxin-allopumiliotoxin class, and a variety of tricyclic alkaloids, including pyrrolizidine oximes, pseudophrynamines, cyclopentaquinolizidines and coccinellines. Most of these alkaloids have been detected and characterized from neotropical dendrobatid frogs. Pumiliotoxins also occur in one genus of Australian myobatrachid frogs, in one genus of South American bufonid toads and in one genus of Madagascan mantellid frogs. It appears all frog skin alkaloids have a dietary origin, being taken up and sequestered unchanged into skin glands. Ants, beetles and millipedes appear to be the source of certain frog skin alkaloids. Decahydroquinolines have now been discovered in ants. The origin of the batrachotoxins, histrionicotoxins, pumiliotoxins, and epibatidines found in frog skin remains a mystery. Structures have now been determined for a 1,4-disubstituted quinolizidine, a trisubstituted indolizidine, a novel tricyclic alkaloid related to the coccinellines, a dimeric decahydroquinoline, a set of nineteen-carbon decahydroquinolines from frogs and ants and an oxirane-containing allopumiliotoxin. Spiropyrrolizidine oximes, pseudophrynaminol, a series of tropane alkaloids (potential muscarinic/nicotinic agonists) and a methylisooxazole analog (epiboxidine) of the potent nicotinic analgetic epibatidine have been synthesized for biological evaluation.