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 journalArticle

60 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)8161-8171
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number17
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

Fingerprint

Tubulin Modulators
Chemotherapy
Tubulin
Cytotoxicity
Bearings (structural)
Cells
Drug Therapy
Cell Line
Prostate
Neoplasms
Carcinoma
combretastatin
benzosuberene

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

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 journalArticle

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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