Anticancer potential of indirubins in medicinal chemistry: Biological activity, structural modification, and structure-activity relationship

  • Eur J Med Chem. 2021 Nov 5:223:113652. doi: 10.1016/j.ejmech.2021.113652.
Hezhen Wang  1 ,  Zhiyuan Wang  1 ,  Chunyong Wei  1 ,  Jing Wang  1 ,  Yingshu Xu  1 ,  Guohui Bai  2 ,  Qizheng Yao  3 ,  Lei Zhang  4 ,  Yongzheng Chen  5
Affiliations
  • 1. Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, 6 West Xuefu Road, Zunyi, 563000, PR China.
  • 2. Key Laboratory of Oral Disease of Higher Schools in Guizhou Province, Zunyi Medical University, 6 West Xuefu Road, Zunyi, 563000, PR China. Electronic address: [email protected].
  • 3. School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, PR China. Electronic address: [email protected].
  • 4. Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, 6 West Xuefu Road, Zunyi, 563000, PR China. Electronic address: [email protected].
  • 5. Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Key Laboratory of Basic Pharmacology of Ministry of Education, School of Pharmacy, Zunyi Medical University, 6 West Xuefu Road, Zunyi, 563000, PR China. Electronic address: [email protected].
PMID: 34161865 DOI: 10.1016/j.ejmech.2021.113652
Abstract

Indirubin is the crucial ingredient of Danggui Longhui Wan and Qing-Dai, traditional Chinese medicine herbal formulas used for the therapy of chronic myelocytic leukemia in China for hundreds of years. Although the monomeric indirubin has been used in China for the treatment human chronic myelocytic leukemia. However, due to low water solubility, poor pharmacokinetic properties and low therapeutic effects are the major obstacle, and had significantly limited its clinical application. Consequently, the attractive Anticancer profile of indirubin has enthused numerous researchers to discover novel indirubin derivatives with improved pharmacodynamic activity as well as good pharmacokinetic property. In this paper, we comprehensively review the recent progress of Anticancer potential of indirubins, structural modification and structure-activity relationship, which may provide useful direction for the further development of novel indirubins with improved pharmacological profiles for the treatment of various types of Cancer.

Keywords
Anticancer activity; Bisindole alkaloid; Indirubin; Mechanism; Structural modification; Structure-activity relationship.