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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Synthesis of Combretastatin A-4 Analogs and their Biological Activities

Author(s): Agnieszka Siebert, Monika Gensicka, Grzegorz Cholewinski and Krystyna Dzierzbicka

Volume 16, Issue 8, 2016

Page: [942 - 960] Pages: 19

DOI: 10.2174/1871520616666160204111832

Price: $65


Combretastatin A-4 (CA-4) is a natural product, which consists of two phenyl rings, linked by an ethylene bridge. CA-4, inhibitor of polymerization of tubulin to microtubules, possesses a strong antitumor and anti-vascular properties both in vitro and in vivo. Previous studies showed that disodium phosphate salt of CA-4, a water-soluble prodrug is well tolerated at therapeutically useful doses. However, it should be noted that the cis-configuration of the double bond and the 3,4,5-trimethoxy group on ring A is necessary for the biological activity of CA-4. Structure of CA-4 renders the compound readily susceptible to isomerization, which reduces the potency and bioavailability. To circumvent this problem, a lot of scientists in the world synthesized a series of cis-restricted CA-4 analogs, where the double bond has been replaced by introduction of non-heterocyclic groups or heterocyclic groups like β -lactam and oxadiazole. This paper reviews the most important approaches in analogs of combretastatin synthesis and presents structure-reactivity relationships for these compounds.

Keywords: Combretastatin A-4, CA-4, Inhibitors of angiogenesis, Synthesis; Biological activity, Cancer therapy.

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