Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene and derived amino acid amides

George Pettit, Collin R. Anderson, Delbert L. Herald, M. Katherine Jung, Debbie J. Lee, Ernest Hamel, Robin Pettit

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

An efficient synthesis of 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the α-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI50 = 10-2-10-3 μg/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.

Original languageEnglish (US)
Pages (from-to)525-531
Number of pages7
JournalJournal of Medicinal Chemistry
Volume46
Issue number4
DOIs
StatePublished - Feb 13 2003

Fingerprint

Stilbenes
Amides
Antineoplastic Agents
Amines
Amino Acids
Tubulin
Cells
Mitotic Index
Colchicine
Cell growth
Polymerization
Acetic Acid
Zinc
Neoplasms
Animals
Salts
Cell Line
Growth

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene and derived amino acid amides. / Pettit, George; Anderson, Collin R.; Herald, Delbert L.; Katherine Jung, M.; Lee, Debbie J.; Hamel, Ernest; Pettit, Robin.

In: Journal of Medicinal Chemistry, Vol. 46, No. 4, 13.02.2003, p. 525-531.

Research output: Contribution to journalArticle

@article{d107c96cdd3c4b88b9a347782c3ac056,
title = "Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene and derived amino acid amides",
abstract = "An efficient synthesis of 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the α-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI50 = 10-2-10-3 μg/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.",
author = "George Pettit and Anderson, {Collin R.} and Herald, {Delbert L.} and {Katherine Jung}, M. and Lee, {Debbie J.} and Ernest Hamel and Robin Pettit",
year = "2003",
month = "2",
day = "13",
doi = "10.1021/jm020204l",
language = "English (US)",
volume = "46",
pages = "525--531",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene and derived amino acid amides

AU - Pettit, George

AU - Anderson, Collin R.

AU - Herald, Delbert L.

AU - Katherine Jung, M.

AU - Lee, Debbie J.

AU - Hamel, Ernest

AU - Pettit, Robin

PY - 2003/2/13

Y1 - 2003/2/13

N2 - An efficient synthesis of 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the α-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI50 = 10-2-10-3 μg/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.

AB - An efficient synthesis of 3,4-methylenedioxy-5,4′-dimethoxy-3′-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the α-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI50 = 10-2-10-3 μg/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.

UR - http://www.scopus.com/inward/record.url?scp=0037434583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037434583&partnerID=8YFLogxK

U2 - 10.1021/jm020204l

DO - 10.1021/jm020204l

M3 - Article

VL - 46

SP - 525

EP - 531

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 4

ER -