摘要
天然药物已从植物、微生物种和海洋生物中鉴定了许多生物活性化合物。这些化合物现大量用作治疗方案药物,而其他天然产生的化学实体给设计非天然药物带来启发,或已完成结构修饰以得到半合成相似物。在过去的十年中,实验证明的Hedgehog(Hh)信号通路的异常活化与多种肿瘤相关,这促使人们研究天然化合物调节这个信号级联的能力。结果,许多天然来源的化合物显示了对Hh信号通路中一个或多个部分的抑制能力,如Smoothened(Smo)和下游效应因子Gli。另一方面,只有少数的天然化合物能够刺激同一途径。本文是对具有干预Hh信号系统的局部以对其造成抑制的活性的天然原料(主要是植物)提取物的调查报告。
关键词: 细胞凋亡,生物活性指导的分离,癌细胞,细胞毒性,Gli1介导的转录活性,Hedgehog抑制剂,Hedgehog信号通路,天然化合物,小分子,构效关系分析,合成,四环素控制的Gli1表达试验。
Current Medicinal Chemistry
Title:Targeting the Hedgehog Signaling Pathway with Small Molecules from Natural Sources
Volume: 22 Issue: 35
Author(s): E. Petricci and F. Manetti
Affiliation:
关键词: 细胞凋亡,生物活性指导的分离,癌细胞,细胞毒性,Gli1介导的转录活性,Hedgehog抑制剂,Hedgehog信号通路,天然化合物,小分子,构效关系分析,合成,四环素控制的Gli1表达试验。
摘要: Natural products drug discovery has allowed the identification of many biologically active compounds from plants, microbial species, and marine organisms. A significant number of these compounds are currently used as drugs in therapeutic protocols, while other naturally occurring chemical entities gave suggestions for designing nonnatural-productderived drugs or have been modified in their structure to have semi-synthetic analogues. In the last decade, experimental evidence that correlated the aberrant activation of the Hedgehog (Hh) signaling pathway with many types of cancer, prompted the researchers to check natural compounds for their ability to modulate this signaling cascade. As a result, many compounds from natural sources showed inhibitory activity toward one or more of the Hh signaling pathway components, such as Smoothened (Smo) and the downstream effectors Gli. On the other hand, only a few natural compounds were able to stimulate the same pathway. This review reports a survey of the compounds extracted from natural sources (especially plants) that showed activity in inhibiting the Hh signaling machinery by interfering with its components.
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Cite this article as:
E. Petricci and F. Manetti , Targeting the Hedgehog Signaling Pathway with Small Molecules from Natural Sources, Current Medicinal Chemistry 2015; 22 (35) . https://dx.doi.org/10.2174/0929867322666150904111042
DOI https://dx.doi.org/10.2174/0929867322666150904111042 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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