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Synthesis and biological evaluation of cis-restrained carbocyclic combretastatin A-4 analogs: Influence of the ring size and saturation on cytotoxic properties.

Abstract：

:Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall activity of the drug candidates. Herein, we report the preparation of cis-restrained carbocyclic analogs of CA-4. The compounds, which differ by the size and hybridization of the carbocyclic ring have been evaluated for their cytotoxic properties and their ability to inhibit tubulin polymerization. Biological data, supported by molecular docking studies, identified cyclobutenyl and cyclobutyl derivatives of the natural product as highly promising drug candidates.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Nowikow C,Fuerst R,Kauderer M,Dank C,Schmid W,Hajduch M,Rehulka J,Gurska S,Mokshyna O,Polishchuk P,Zupkó I,Dzubak P,Rinner U

doi

10.1016/j.bmc.2019.07.048

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

115032

issue

19

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(19)30372-4

journal_volume

27

pub_type

杂志文章

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