Acetyl Analogs of the Anticancer Agent Combretastatin A4: Synthesis and Biological Evaluation

Faculty Mentor(s)

Dr. Moses Lee, Hope College
Dr. Greg Fraley, Hope College
Dr. Balaji Babu, Hope College
Dr. Dereje Desta, Hope College
Dr. Sameer Chavda, Hope College

Document Type


Publication Date



The authors thank Conjura Pharm, LLC and The Arnold and Mabel Beckman Foundation (RS) for support.


Combretastatin A4 (CA-4) is a powerful agent that causes microtubule depolymerization in cells and is known to possess potent cytotoxic activity against the growth of cancer cells in culture. Due to its poor solubility in water, a phosphate-containing prodrug was developed, and it is presently undergoing phase II/III clinical trials for human cancer treatment. In this study, twenty new and theoretically more water-soluble acetyl analogs of CA-4 were designed and synthesized. Molecular modeling and single crystal x-ray crystallography studies showed that the acetyl-analogs have the same twisted conformation as the lead compound, CA-4. Cytotoxicity studies indicated that three analogs were particularly active, and a cell-based assay indicated that at least one of those has the same mechanism (microtubule depolymerization) as CA-4. Finally, in vivo mice studies demonstrated that the acetyl analog most similar to CA-4 demonstrated significant antitumor activity without showing any toxicity to healthy animals.

This document is currently not available here.