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

doi:10.1021/np070377j

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

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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 language	English (US)
Pages (from-to)	313-320
Number of pages	8
Journal	Journal of Natural Products
Volume	71
Issue number	3
DOIs	https://doi.org/10.1021/np070377j
State	Published - Mar 2008

ASJC Scopus subject areas

Analytical Chemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

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Siles, R., Ackley, J. F., Hadimani, M. B., Hall, J. J., Mugabe, B. E., Guddneppanavar, R., Monk, K. A., Chapuis, J., Pettit, G., Chaplin, D. J., Edvardsen, K., Trawick, M. L., Garner, C. M., & 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

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

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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.",

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year = "2008",

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doi = "10.1021/np070377j",

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AU - Hall, John J.

AU - Mugabe, Benon E.

AU - Guddneppanavar, Rajsekhar

AU - Monk, Keith A.

AU - Chapuis, Jean

AU - Pettit, George

AU - Chaplin, David J.

AU - Edvardsen, Klaus

AU - Trawick, Mary Lynn

AU - Garner, Charles M.

AU - Pinney, Kevin G.

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

Abstract

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