Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications

Molecules. 2020 May 31;25(11):2560. doi: 10.3390/molecules25112560.


Combretastatins are a class of closely related stilbenes (combretastatins A), dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D) found in the bark of Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow. Some of the compounds in this series have been shown to be among the most potent antitubulin agents known. Due to their structural simplicity many analogs have also been synthesized. Combretastatin A4 phosphate is the most frequently tested compounds in preclinical and clinical trials. It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. In addition, in vitro and in vivo studies on combretastatins have determined that these compounds also have antioxidant, anti-inflammatory and antimicrobial effects. Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects. In this review, a synopsis of the recent literature exploring the combretastatins, their potential effects and nanoformulations as lead compounds in clinical applications is provided.

Keywords: combretaceae; combretastatins; drug discovery; nanoformulation; natural compound; structure-activity relationships; tubulin inhibitors..

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antioxidants / chemistry
  • Antiparasitic Agents / pharmacology
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation
  • Combretum / chemistry
  • Drug Delivery Systems
  • HT29 Cells
  • Humans
  • Melanoma, Experimental / metabolism
  • Solubility
  • Stereoisomerism
  • Stilbenes / chemistry*
  • Stilbenes / pharmacology
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tubulin Modulators / pharmacology
  • Water / chemistry


  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Antiparasitic Agents
  • Stilbenes
  • Tubulin
  • Tubulin Modulators
  • combretastatin B-1
  • Water
  • fosbretabulin