Vine K L, Matesic L, Locke J M, Ranson M, Skropeta D
School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
Anticancer Agents Med Chem. 2009 May;9(4):397-414. doi: 10.2174/1871520610909040397.
Isatin (1H-indole-2,3-dione) and its derivatives demonstrate a diverse array of biological and pharmacological activities including anticonvulsant, antibacterial, antifungal, antiviral and anticancer properties. This broad spectrum of biochemical targets has been facilitated by the synthetic versatility of isatin, which has allowed the generation of a large number of structurally diverse derivatives including analogues derived from substitution of the aryl ring, and/or derivatisation of the isatin nitrogen and C2/C3 carbonyl moieties. The recent FDA approval of the oxindole sunitinib malate, as a kinase inhibitor for the treatment of advanced renal carcinoma and gastrointestinal stromal tumours, underscores the increasing interest in isatins as a new class of antineoplastic agents. In addition to potent kinase inhibition, the mechanism of action of other isatin derivatives includes the inhibition and/or modulation of proteases, translation initiation, neo-vascularisation and tubulin polymerisation. It was therefore the objective of this review to systematically evaluate the cytotoxic and anticancer properties of various substituted isatins and collate these findings to be used as a guide for future structure-activity relationship and mode of action studies. This is the first review to comprehensively discuss the in vitro and in vivo anticancer activities of isatin and its substituted derivatives.
异吲哚酮（1H-吲哚-2,3-二酮）及其衍生物具有多种生物和药理活性，包括抗惊厥、抗菌、抗真菌、抗病毒和抗癌特性。异吲哚酮的合成多样性促进了其广泛的生化靶点，这使得能够生成大量结构多样的衍生物，包括芳环取代衍生物以及异吲哚酮氮和C2/C3羰基部分的衍生化产物。最近美国食品药品监督管理局（FDA）批准了氧化吲哚苹果酸舒尼替尼作为一种激酶抑制剂用于治疗晚期肾癌和胃肠道间质瘤，这凸显了人们对异吲哚酮作为一类新型抗肿瘤药物的兴趣日益浓厚。除了强效的激酶抑制作用外，其他异吲哚酮衍生物的作用机制还包括抑制和/或调节蛋白酶、翻译起始、新血管形成和微管蛋白聚合。因此，本综述的目的是系统评估各种取代异吲哚酮的细胞毒性和抗癌特性，并整理这些发现，以作为未来构效关系和作用方式研究的指南。这是第一篇全面讨论异吲哚酮及其取代衍生物的体外和体内抗癌活性的综述。
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