Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents

Rogelio Siles, J. Freeland Ackley, Mallinath B. Hadimani, John J. Hall, Benon E. Mugabe, Rajsekhar Guddneppanavar, Keith A. Monk, Jean Chapuis, George Pettit, David J. Chaplin, Klaus Edvardsen, Mary Lynn Trawick, Charles M. Garner, Kevin G. Pinney

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2′,3′-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI50 = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC50 = 2.8 μM). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.

Original languageEnglish (US)
Pages (from-to)313-320
Number of pages8
JournalJournal of Natural Products
Volume71
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Bearings (structural)
Stilbenes
stilbenes
Tubulin
tubulin
blood vessels
Blood Vessels
Tumors
stilbenoids
neoplasms
nitrogen
Cytotoxicity
Bioactivity
Biological Products
amines
blood flow
Amines
inhibitory concentration 50
cytotoxicity
bioactive properties

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Siles, R., Ackley, J. F., Hadimani, M. B., Hall, J. J., Mugabe, B. E., Guddneppanavar, R., ... Pinney, K. G. (2008). Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents. Journal of Natural Products, 71(3), 313-320. https://doi.org/10.1021/np070377j

Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents. / Siles, Rogelio; Ackley, J. Freeland; Hadimani, Mallinath B.; Hall, John J.; Mugabe, Benon E.; Guddneppanavar, Rajsekhar; Monk, Keith A.; Chapuis, Jean; Pettit, George; Chaplin, David J.; Edvardsen, Klaus; Trawick, Mary Lynn; Garner, Charles M.; Pinney, Kevin G.

In: Journal of Natural Products, Vol. 71, No. 3, 03.2008, p. 313-320.

Research output: Contribution to journalArticle

Siles, R, Ackley, JF, Hadimani, MB, Hall, JJ, Mugabe, BE, Guddneppanavar, R, Monk, KA, Chapuis, J, Pettit, G, Chaplin, DJ, Edvardsen, K, Trawick, ML, Garner, CM & Pinney, KG 2008, 'Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents', Journal of Natural Products, vol. 71, no. 3, pp. 313-320. https://doi.org/10.1021/np070377j
Siles, Rogelio ; Ackley, J. Freeland ; Hadimani, Mallinath B. ; Hall, John J. ; Mugabe, Benon E. ; Guddneppanavar, Rajsekhar ; Monk, Keith A. ; Chapuis, Jean ; Pettit, George ; Chaplin, David J. ; Edvardsen, Klaus ; Trawick, Mary Lynn ; Garner, Charles M. ; Pinney, Kevin G. / Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents. In: Journal of Natural Products. 2008 ; Vol. 71, No. 3. pp. 313-320.
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