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 | |
| State | 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
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
}
TY - JOUR
T1 - Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitors of tubulin polymerization in cancer chemotherapy
AU - Sriram, Madhavi
AU - Hall, John J.
AU - Grohmann, Nathan C.
AU - Strecker, Tracy E.
AU - Wootton, Taylor
AU - Franken, Andreas
AU - Trawick, Mary Lynn
AU - Pinney, Kevin G.
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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).
AB - 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).
KW - Benzosuberenes
KW - Cancer Chemotherapy
KW - Combretastatins
KW - Dihydronaphthalenes
KW - Tubulin
KW - Vascular disrupting agents
UR - http://www.scopus.com/inward/record.url?scp=50349092736&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50349092736&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2008.07.050
DO - 10.1016/j.bmc.2008.07.050
M3 - Article
C2 - 18722127
AN - SCOPUS:50349092736
VL - 16
SP - 8161
EP - 8171
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 17
ER -