Abstract
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.
Highlights
Throughout the ages humans have utilized Nature, especially plants, to meet their basic to complex needs such the production of foodstuffs, shelter, clothing, means of transportation, fertilizers, flavors, fragrances and medicines as well
It was reported that administration of combretastatin A1 reported to intensely inhibit endothelial cell migration and capillary tube formation by inhibiting phosphate at 150 mg/kg dose to vascularized murine colon adenocarcinoma (MAC 29) caused a the VE-cadherin/β-catenin/Akt signaling pathway, thereby causing vascular collapse and tumor strong decrease in vascular volume after 2 h [48]
These findings reveal that combination of morphological and functional changes in endothelial cells cause the rapid decrease in tumor blood flow after the treatment of combretastatin-A4 phosphate (CA-4P) in vivo
Summary
Throughout the ages humans have utilized Nature, especially plants, to meet their basic to complex needs such the production of foodstuffs, shelter, clothing, means of transportation, fertilizers, flavors, fragrances and medicines as well. Evaluation of natural products as anticancer agents was recognized in the 1950s by the U.S National Cancer. Natural Products Branch and succeeded in the isolation of a compound named combretastatin [5]. Lam., whose prominent structural feature is a macrocyclic lactone [9,10,11,12,13] What makes this class of compounds (primarily the A series) rather more interesting than other secondary metabolites is their significant antimitotic and antiproliferative activity. The activity of combrestatins is closely related to their stereoisomeric configurations Both natural and synthetic derivatives with diverse configurations and functional groups have been a main subject of cancer chemotherapy clinical trials in recent years [14,15]. The aim of this study is to review the occurrence, bioactivities, structural varieties and structure activity relationship studies of combretastatins
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