Antineoplastic agents 440. Asymmetric synthesis and evaluation of the combretastatin A-1 SAR probes (1S,2S)- and (1R,2R)-1,2-dihydroxy-1-(2',3'-dihydroxy-4'-methoxyphenyl)-2-(3'' ,4'',5''-trimethoxyphenyl)-ethane

George Pettit, John W. Lippert, Delbert L. Herald, Ernest Hamel, Robin Pettit

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 ED50 values of 3.9 and 2.9 μg/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 ED50 0.25 μg/mL).

Original languageEnglish (US)
Pages (from-to)969-974
Number of pages6
JournalJournal of Natural Products
Volume63
Issue number7
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Stilbenes
ethane
glycols
Ethane
antineoplastic agents
Antineoplastic Agents
Combretum
Cells
Anti-Bacterial Agents
Lymphoid Leukemia
Cell Line
Hydroxylation
synthesis
stilbenes
Cell growth
Structure-Activity Relationship
Tubulin
Isomers
Microorganisms
Combretum caffrum

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

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title = "Antineoplastic agents 440. Asymmetric synthesis and evaluation of the combretastatin A-1 SAR probes (1S,2S)- and (1R,2R)-1,2-dihydroxy-1-(2',3'-dihydroxy-4'-methoxyphenyl)-2-(3'' ,4'',5''-trimethoxyphenyl)-ethane",
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 ED50 values of 3.9 and 2.9 μg/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 ED50 0.25 μg/mL).",
author = "George Pettit and Lippert, {John W.} and Herald, {Delbert L.} and Ernest Hamel and Robin Pettit",
year = "2000",
doi = "10.1021/np0000623",
language = "English (US)",
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T1 - Antineoplastic agents 440. Asymmetric synthesis and evaluation of the combretastatin A-1 SAR probes (1S,2S)- and (1R,2R)-1,2-dihydroxy-1-(2',3'-dihydroxy-4'-methoxyphenyl)-2-(3'' ,4'',5''-trimethoxyphenyl)-ethane

AU - Pettit, George

AU - Lippert, John W.

AU - Herald, Delbert L.

AU - Hamel, Ernest

AU - Pettit, Robin

PY - 2000

Y1 - 2000

N2 - 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 ED50 values of 3.9 and 2.9 μg/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 ED50 0.25 μg/mL).

AB - 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 ED50 values of 3.9 and 2.9 μg/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 ED50 0.25 μg/mL).

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