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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
1996-9-26
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pubmed:abstractText |
Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) positions of ellipticine. The ellipticine-estradiol conjugates were evaluated for their abilities to bind to estrogen receptors, to inhibit topoisomerase II, and for their cytotoxicities in human cancer cell lines. Conjugates 3 and 5 displayed weak binding affinities of 0.132 and 0.303 for the estrogen receptor (relative to estradiol = 100), while conjugate 4 did not show any detectable binding to the estrogen receptor. Compound 3 was a moderate inhibitor of topoisomerase II (IC50 24.1 microM), while 4 and 5 were inactive. Conjugate 3 was consistently more cytotoxic (GI50 values 1-10 microM) than compounds 4 and 5 (GI50 values 10-100 microM) in a variety of human cancer cell lines. None of the compounds displayed any selectivity for estrogen-receptor positive cell lines, which probably reflects their weak affinities for estrogen receptors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3367-74
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8765520-Antineoplastic Agents,
pubmed-meshheading:8765520-Breast Neoplasms,
pubmed-meshheading:8765520-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:8765520-Cell Survival,
pubmed-meshheading:8765520-Central Nervous System Neoplasms,
pubmed-meshheading:8765520-Drug Design,
pubmed-meshheading:8765520-Ellipticines,
pubmed-meshheading:8765520-Estradiol,
pubmed-meshheading:8765520-Female,
pubmed-meshheading:8765520-Humans,
pubmed-meshheading:8765520-Kidney Neoplasms,
pubmed-meshheading:8765520-Leukemia,
pubmed-meshheading:8765520-Lung Neoplasms,
pubmed-meshheading:8765520-Male,
pubmed-meshheading:8765520-Melanoma,
pubmed-meshheading:8765520-Ovarian Neoplasms,
pubmed-meshheading:8765520-Placenta,
pubmed-meshheading:8765520-Pregnancy,
pubmed-meshheading:8765520-Prostatic Neoplasms,
pubmed-meshheading:8765520-Receptors, Estrogen,
pubmed-meshheading:8765520-Structure-Activity Relationship,
pubmed-meshheading:8765520-Topoisomerase II Inhibitors,
pubmed-meshheading:8765520-Tumor Cells, Cultured
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pubmed:year |
1996
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pubmed:articleTitle |
Design, synthesis, and biological evaluation of ellipticine-estradiol conjugates.
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pubmed:affiliation |
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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