title: Synthesis of Combretastatin A-4 Analogs and their Biological Activities.
abstract: 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a lot of scientists in the world synthesized a series of cis-restricted CA-4 analogs, where the double bond has been replaced by introduction of non-heterocyclic groups or heterocyclic groups like β -lactam and oxadiazole.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.
authors: Agnieszka
authors: A
authors: Siebert
authors: Monika
authors: M
authors: Gensicka
authors: Grzegorz
authors: G
authors: Cholewinski
authors: Faculty of Chemistry, Department of Organic Chemistry, Gdansk University of Technology, G. Narutowicza St 11/12, 80-233 Gdansk, Poland.
authors: Krystyna
authors: K
authors: Dzierzbicka
keywords: CA-4; Cancer therapy; Combretastatin A-4; Inhibitors of angiogenesis; Synthesis; Biological activity