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Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents

Monk, KA ; Siles, R ; Hadimani, MB ; Mugabe, BE ; Ackley, JF ; Studerus, SW ; Edvardsen, Klaus LU ; Trawick, ML ; Garner, CM and Rhodes, MR , et al. (2006) In Bioorganic & Medicinal Chemistry 14(9). p.3231-3244
Abstract
A series of analogs with nitro or serinamide substituents at the C-2'-, C-5'-, or C-C-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization. The synthesis of these analogs typically featured a Wittig reaction between a suitably functionalized arylaldehyde and an arylphosphonium salt followed by separation of the resultant F and Z-isomers. several of these nitrogen-modified CA4 derivatives (both amino and nitro) demonstrate significant inhibition of tubulin assembly as well as cytotoxicity and in vivo blood flow reduction. 2'-Aminostilbenoid 7 and... (More)
A series of analogs with nitro or serinamide substituents at the C-2'-, C-5'-, or C-C-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization. The synthesis of these analogs typically featured a Wittig reaction between a suitably functionalized arylaldehyde and an arylphosphonium salt followed by separation of the resultant F and Z-isomers. several of these nitrogen-modified CA4 derivatives (both amino and nitro) demonstrate significant inhibition of tubulin assembly as well as cytotoxicity and in vivo blood flow reduction. 2'-Aminostilbenoid 7 and 2'-amino-3'-hydroxystilbenoid 29 proved to be the most active in this series. Both compounds, 7 and 29, have the potential for further pro-drug modification and development as vascular disrupting agents for treatment of solid tumor cancers and certain ophthalmological diseases. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
vascular disrupting agents, pro-drug constructs, anti-cancer, inhibitors of tubulin assembly, combretastatin, tubilin
in
Bioorganic & Medicinal Chemistry
volume
14
issue
9
pages
3231 - 3244
publisher
Elsevier
external identifiers
  • wos:000236591200037
  • pmid:16442292
  • scopus:33644988592
  • pmid:16442292
ISSN
0968-0896
DOI
10.1016/j.bmc.2005.12.033
language
English
LU publication?
yes
id
55ca167d-06d2-4ff2-aa85-003839cf46b8 (old id 414637)
date added to LUP
2016-04-01 11:52:20
date last changed
2021-09-15 05:15:41
@article{55ca167d-06d2-4ff2-aa85-003839cf46b8,
  abstract     = {A series of analogs with nitro or serinamide substituents at the C-2'-, C-5'-, or C-C-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization. The synthesis of these analogs typically featured a Wittig reaction between a suitably functionalized arylaldehyde and an arylphosphonium salt followed by separation of the resultant F and Z-isomers. several of these nitrogen-modified CA4 derivatives (both amino and nitro) demonstrate significant inhibition of tubulin assembly as well as cytotoxicity and in vivo blood flow reduction. 2'-Aminostilbenoid 7 and 2'-amino-3'-hydroxystilbenoid 29 proved to be the most active in this series. Both compounds, 7 and 29, have the potential for further pro-drug modification and development as vascular disrupting agents for treatment of solid tumor cancers and certain ophthalmological diseases.},
  author       = {Monk, KA and Siles, R and Hadimani, MB and Mugabe, BE and Ackley, JF and Studerus, SW and Edvardsen, Klaus and Trawick, ML and Garner, CM and Rhodes, MR and Pettit, GR and Pinney, KG},
  issn         = {0968-0896},
  language     = {eng},
  number       = {9},
  pages        = {3231--3244},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry},
  title        = {Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents},
  url          = {http://dx.doi.org/10.1016/j.bmc.2005.12.033},
  doi          = {10.1016/j.bmc.2005.12.033},
  volume       = {14},
  year         = {2006},
}