Marine indole alkaloids: potential new drug leads for the control of depression and anxiety.
Marine indole alkaloids: potential new drug leads for the control of depression and anxiety.
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DOI：
10.1021/cr900211p
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发表时间：
2010-08-11
期刊：
影响因子：
62.1
通讯作者：
Hamann, Mark T.
中科院分区：
文献类型：
--
作者：
Kochanowska-Karamyan, Anna J.;Hamann, Mark T.
在过去的50年里，人们在寻找新的生物活性化合物的过程中探索了海洋环境，成为一种非常重要和丰富的有效分子来源和据报道具有广泛活动范围的药物线索。生物碱是天然产物中最大的一类，由陆地和海洋生物在所有进化水平上合成。生物碱通常以几种主要化合物和少数次要化合物的混合物形式存在于生物体中，这些化合物具有相同的生物合成来源，只是功能基团不同。这组化合物显然已经进化为抵抗捕食者的防御机制，因此生物碱通常是高度有效和有毒的分子。1海洋无脊椎动物已被证明是活性分子的杰出来源，其中最有希望的是吲哚生物碱。尽管许多海洋生物碱与内源胺(5-羟色胺、多巴胺或组胺)非常相似，但它们与各种神经靶标的潜在亲和力以及由此对动物行为的影响几乎没有被开发。吲哚生物碱、它们的活性、合成以及在医学上的潜在用途已经在几篇文章中进行了综述。2在这篇综述中，我们提供了当前和潜在的药物信息，包括小分子天然吲哚生物碱、它们的生物学性质、构效关系研究，特别是它们在治疗神经疾病方面的潜力。
The marine environment has been explored in the search for new bioactive compounds over the last 50 years, becoming a highly important and rich source of potent molecules and drug leads reported to possess a wide scope of activities. Alkaloids constitute one of the largest classes of natural products and are synthesized by terrestrial and marine organisms on all evolutionary levels. Alkaloids are usually present in an organism as a mixture consisting of several major and a few minor compounds of the same biosynthetic origin and differing only in functional groups. This group of compounds has apparently evolved as a defense mechanism against predators and as a result alkaloids are often highly potent and toxic molecules. 1 Marine invertebrates have proven to be an outstanding source of active molecules, one of the most promising being indole alkaloids. Although many of these marine alkaloids closely resemble the endogenous amines (serotonin, dopamine, or histamine), their potential affinity to various neurological targets and consequential impact on animal behavior is virtually unexplored.Indole alkaloids, their activity, synthesis, and potential use in medicine have been already reviewed in several articles. 2 In this review, we provide information on current and potential pharmaceuticals including small molecule natural indole alkaloids, their biological properties, structure-activity relationship studies, and especially their potential for the treatment of neurological disorders.
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