Abstract |
The synthetic (E)-isomer (3b) of natural combretastatin A-1 (1a) isolated from the African bushwillow Combretum caffrum was the focus of chiral hydroxylation (Sharpless) reactions as part of a structure-activity relationship study. The resulting (R,R)- and (S,S, )-diols (6 and 7) and synthetic intermediates were evaluated against a series of cancer cell lines, microorganisms, and tubulin. Chiral diols 6 and 7 showed increased activity against the P-388 murine lymphocytic leukemia cell line with ED(50) values of 3.9 and 2.9 microg/mL, respectively, when compared to the precursor (E)- stilbene 3b. In contrast, (E)- stilbene 3b exhibited more potent antibiotic activity than the chiral diols (6 and 7). Both diols, (R,R)-6 and (S, S)-7, displayed less cancer cell growth inhibition and less antibiotic activity than did natural combretastatin A-1 (1a) (P-388 ED(50) 0.25 microg/mL).
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Authors | G R Pettit, J W Lippert 3rd, D L Herald, E Hamel, R K Pettit |
Journal | Journal of natural products
(J Nat Prod)
Vol. 63
Issue 7
Pg. 969-74
(Jul 2000)
ISSN: 0163-3864 [Print] United States |
PMID | 10924176
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- 1,2-dihydroxy-1-(2',3'-dihydroxy-4'-methoxyphenyl)-2-(3'',4'',5''-trimethoxyphenyl)ethane
- Antineoplastic Agents, Phytogenic
- Ethylene Glycols
- Molecular Probes
- Stilbenes
- combretastatin A-1
- Guaiacol
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(chemical synthesis, chemistry, pharmacology)
- Drug Screening Assays, Antitumor
- Ethylene Glycols
(chemical synthesis, chemistry, pharmacology)
- Guaiacol
(analogs & derivatives, chemical synthesis, chemistry, pharmacology)
- Humans
- Mice
- Microbial Sensitivity Tests
- Molecular Probes
- Stereoisomerism
- Stilbenes
(chemistry)
- Structure-Activity Relationship
- Trees
(chemistry)
- Tumor Cells, Cultured
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