Synthetic progress and anti-leukemic research on indirubin analogues: a review since 2010

Indirubin, an active component of the traditional Chinese medicine Indigo Naturalis, has drawn significant attention owing to its remarkable anti-leukemia activity. Nevertheless, it presents issues such as limited natural resources, poor solubility, and potential toxicity, which impede its clinical application. In recent years, within the research realm of indirubins, the efficient synthetic strategies and the exploration in the treatment of leukemia have remained the central research focuses in this field. This article comprehensively reviews the research advancements of indirubin derivatives in synthesis strategies and anti-leukemia effects since 2010s. Firstly, in this review, the synthetic methods of indirubin derivatives are categorized into two main types: chemical synthesis and bio & biomimetic synthesis. Among these, chemical methods assume a dominant position. These chemical synthesis approaches encompass acid-catalyze, organophosphorus-catalyzed, metal-catalyzed reactions, and one-step reduction reactions using KBH4. Secondly, based on the modification sites within the structure of indirubin, this paper undertakes a classified review of its derivatives and further delves deeply into the anti-leukemia activities of these derivatives. Additionally, we also discuss the future development directions of synthesizing indirubin derivatives and explore their structure-activity relationships in the context of anti-leukemia research. We firmly believe that this review can offer information support for scientific researchers engaged in the study of indirubin's anti-leukemia effects, thereby facilitating in-depth development.