PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

来自两栖动物和其他天然来源的药理活性化合物

• 批准号: 3875848
• 负责人: J W DALY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3875848
• 关键词: Anura; alkaloids; amidines; analgesics; animal poison; batrachotoxins; chemical binding; chemical structure function; drug metabolism; heart pharmacology; infrared spectrometry; mass spectrometry; muscle pharmacology; neuropharmacology; neurotoxins; nicotinic receptors; piperidine; potassium channel; skin; sodium channel

Natural products have provided a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over two hundred alkaloids have been identified In extracts from amphibian skins. These include batracbotoxins, which are potent activators of sodium channels, histrionicotoxins, Which are noncompetitive blockers of nicotinic receptor channel complexes and of potassium channels, and pumiliotoxins, which have myotonic and cardiotonic activity (iii(- to inhibitory effects on closing of sodium channels. A variety of further alkaloids have, been characterized from dendrobatid frogs. These include new 2,5-disubstituted decahydroquinolizies 5,8-disubstited indolizidines, 6,9-disubstituted quinolizidines, 3,5-disubstituted pyrrolizidines, pumiliotoxins, homopumiliotoxins and allopumilliotoxins. Many of these alkaloids have activity as noncompetitive blockers at muscle-type and ganglionic-type nicotinic receptor-channels. Structures for three tricyclic pyrrolizidinone oximes and O-mothyloximes from a dendrobatid frog have been determined based on analysis by mass spectrometry, infrared spectroscopy and nuclear magnetic resonance spectrometry. A structure for the parent member (C(11)H(13)N(2)Cl(2) ) a new class of analgetic alkaloids has been similarly derived by analysis of an N-acetyl derivative. Characterization of alkaloids in nondendrobatid amphibians indicates that the biosynthetic pathways to certain dendrobatid alkaloids have evolved separately in one lineage (genus) of amphibians from the families Bufonidae, Myobatracidae and Ranidae and in a lineage leading to four genera in the family Dendrobatider. The lack of alkaloid production in captive-raised dendrobatid frogs now appears due to lack of natural environment and/or diet. A peptide (thirty amino acid residues) isolated from mucous secretions of a hylid frog Phyllomedusa bicolor causes profound behavioral depression land stimulates binding of adenosine agonists to brain A(1)-adenosine receptors.

天然产品提供了广泛的生物活性剂， 其中许多具有药理学活动和 治疗潜力。在 来自两栖皮的提取物。其中包括batracbotoxins， 钠通道的有效激活剂，术毒素，是 烟碱受体通道复合物的非竞争阻滞剂和 钾通道和粉状毒素，具有肌动型和心脏。 活性（iii（ - 抑制钠通道关闭的影响。 从树突状的多种多样的生物碱已表征 青蛙。其中包括新的2,5二取代的decahydroquinolizizizizies 5,8-溶解的吲哚衍生物，6,9-二取代的奎诺硅烷， 3,5二取代的吡咯烷，pumiliotoxins，同叶核毒素和 杂菌素毒素。这些生物碱中的许多具有非竞争性活性 肌肉型和神经节型烟碱受体通道的阻滞剂。 三个三环吡咯烷酮的结构 根据质量分析，已经确定了树突叶蛙 光谱，红外光谱和核磁共振 光谱法。母体成员的结构（C（11）H（13）N（2）Cl（2））A 通过对 N-乙酰基衍生物。在非肠齿中的生物碱的表征 两栖动物表明某些树突的生物合成途径 生物碱已在两栖动物的一个谱系（属）中分别演变 一家人Bufonidae，Myobatracidae和Ranidae，并处于领先地位 在家庭Dendrobatider中四属。缺乏生物碱生产 现在由于缺乏自然而出现在俘虏饲养的树枝状青蛙中 环境和/或饮食。分离的肽（三十个氨基酸残基） 从混合青蛙Phyllomedusa双色的粘液分泌物引起了深刻的影响 行为抑郁症土地刺激腺苷激动剂与 脑A（1）腺苷受体。