Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy.
Molecules. 2021 Jul 12;26(14):4228. doi: 10.3390/molecules26144228.
Naturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due to the versatility of the scaffolds and the vast possibilities of appropriate decoration, they have also been regarded as fruitful sources of lead compounds and excellent chemical platforms for the development of bioactive synthetic compounds. Flavone-8-acetic acid (FAA) and 5,6-dimethylxanthone acetic acid (DMXAA) emerged for their antitumour potential due to the induction of cytokines and consequent rapid haemorrhagic necrosis of murine tumour vasculature, and different series of derivatives have been designed thereafter. Although the promising DMXAA failed in phase III clinical trials because of strict species-specificity, a boost in research came from the recent identification of the stimulator of interferon genes (STING), responsible for supporting tumoural innate immune responses, as a possible biological target. Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Undoubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective.
天然存在的类黄酮作为次生代谢物存在于大量被用于医学和食品的植物中，长期以来一直被认为具有多种生物活性，使它们成为治疗不同疾病的有用工具。由于支架的多功能性和适当修饰的巨大可能性，它们也被视为有前途的先导化合物来源和用于开发生物活性合成化合物的优秀化学平台。黄酮-8-乙酸（FAA）和 5,6-二甲基黄嘌呤乙酸（DMXAA）因其诱导细胞因子和随后导致鼠肿瘤血管迅速出血性坏死而具有抗肿瘤潜力而受到关注，此后设计了不同系列的衍生物。尽管有前景的 DMXAA 由于严格的种特异性而在 III 期临床试验中失败，但最近发现干扰素基因刺激物（STING）作为支持肿瘤固有免疫反应的可能生物学靶标，为研究带来了新的动力。因此，在过去十年中，人们对这些基于类黄酮的结构重新产生了兴趣，并合成了新的衍生物，以更深入地了解影响人类细胞所需的分子特征。毫无疑问，这些天然衍生的分子值得进一步研究，并且在抗癌方面仍然具有吸引力。
