Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy

Madhavi Sriram; John J. Hall; Nathan C. Grohmann; Tracy E. Strecker; Taylor Wootton; Andreas Franken; Mary Lynn Trawick; Kevin G. Pinney

doi:10.1016/j.bmc.2008.07.050

Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy

Madhavi Sriram, John J. Hall, Nathan C. Grohmann, Tracy E. Strecker, Taylor Wootton, Andreas Franken, Mary Lynn Trawick, Kevin G. Pinney

Research output: Contribution to journal › Article

61 Scopus citations

Abstract

A novel series of dihydronaphthalene and benzosuberene analogs bearing structural similarity to the combretastatins in terms of 1,2-diarylethene, trimethoxyphenyl, and biaryl functionality has been synthesized. The compounds have been evaluated in regard to their ability to inhibit tubulin assembly and for their cytotoxicity against selected human cancer cell lines. From this series of compounds, benzosuberene analogs 2 and 4 inhibited tubulin assembly at concentrations comparable to that of combretastatin A-4 (CA4) and combretastatin A-1 (CA1). Furthermore, analog 4 demonstrated remarkable cytotoxicity against the three human cancer cell lines evaluated (for example GI₅₀ = 0.0000032 μM against DU-145 prostate carcinoma).

Original language	English (US)
Pages (from-to)	8161-8171
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2008.07.050
Publication status	Published - Sep 1 2008
Externally published	Yes

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Keywords

Benzosuberenes
Cancer Chemotherapy
Combretastatins
Dihydronaphthalenes
Tubulin
Vascular disrupting agents

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Cite this

Sriram, M., Hall, J. J., Grohmann, N. C., Strecker, T. E., Wootton, T., Franken, A., ... Pinney, K. G. (2008). Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy. Bioorganic and Medicinal Chemistry, 16(17), 8161-8171. https://doi.org/10.1016/j.bmc.2008.07.050

Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy. / Sriram, Madhavi; Hall, John J.; Grohmann, Nathan C.; Strecker, Tracy E.; Wootton, Taylor; Franken, Andreas; Trawick, Mary Lynn; Pinney, Kevin G.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 17, 01.09.2008, p. 8161-8171.

Research output: Contribution to journal › Article

Sriram, M, Hall, JJ, Grohmann, NC, Strecker, TE, Wootton, T, Franken, A, Trawick, ML & Pinney, KG 2008, 'Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy', Bioorganic and Medicinal Chemistry, vol. 16, no. 17, pp. 8161-8171. https://doi.org/10.1016/j.bmc.2008.07.050

Sriram, Madhavi ; Hall, John J. ; Grohmann, Nathan C. ; Strecker, Tracy E. ; Wootton, Taylor ; Franken, Andreas ; Trawick, Mary Lynn ; Pinney, Kevin G. / Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 17. pp. 8161-8171.

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abstract = "A novel series of dihydronaphthalene and benzosuberene analogs bearing structural similarity to the combretastatins in terms of 1,2-diarylethene, trimethoxyphenyl, and biaryl functionality has been synthesized. The compounds have been evaluated in regard to their ability to inhibit tubulin assembly and for their cytotoxicity against selected human cancer cell lines. From this series of compounds, benzosuberene analogs 2 and 4 inhibited tubulin assembly at concentrations comparable to that of combretastatin A-4 (CA4) and combretastatin A-1 (CA1). Furthermore, analog 4 demonstrated remarkable cytotoxicity against the three human cancer cell lines evaluated (for example GI50 = 0.0000032 μM against DU-145 prostate carcinoma).",

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10.1016/j.bmc.2008.07.050