Concise syntheses of the abyssinones and discovery of new inhibitors of prostate cancer and MMP-2 expression

Rebecca L. Farmer; Margaret M. Biddle; Antoinette E. Nibbs; Xiaoke Huang; Raymond C. Bergan; Karl A. Scheidt

doi:10.1021/ml100110x

Concise syntheses of the abyssinones and discovery of new inhibitors of prostate cancer and MMP-2 expression

Rebecca L. Farmer
, Margaret M. Biddle
, Antoinette E. Nibbs
, Xiaoke Huang
, Raymond C. Bergan
, Karl A. Scheidt

Cancer Center

Northwestern University
Department of Medicine

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

The first asymmetric syntheses of four members of the abyssinone class of natural products (I, II, III, and IV 4′-OMe) via quinine- or quinidine-derived thiourea-catalyzed intramolecular conjugate additions of β-keto ester alkylidenes are reported. This concise strategy delivers all four natural products and their corresponding antipodes. A preliminary evaluation of all of these small molecules against a metastatic human prostate cancer cell line has identified that these compounds selectively and differentially inhibit cell growth and downregulate the expression of matrix metalloproteinase-2 (MMP-2) at nontoxic concentrations.

Original language	English
Pages (from-to)	400-405
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	1
Issue number	8
DOIs	https://doi.org/10.1021/ml100110x
State	Published - Nov 11 2010

Keywords

Abyssinones
hydrogen-bonding catalysis
MMP-2 expression
prostate cancer

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10.1021/ml100110x

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title = "Concise syntheses of the abyssinones and discovery of new inhibitors of prostate cancer and MMP-2 expression",

abstract = "The first asymmetric syntheses of four members of the abyssinone class of natural products (I, II, III, and IV 4′-OMe) via quinine- or quinidine-derived thiourea-catalyzed intramolecular conjugate additions of β-keto ester alkylidenes are reported. This concise strategy delivers all four natural products and their corresponding antipodes. A preliminary evaluation of all of these small molecules against a metastatic human prostate cancer cell line has identified that these compounds selectively and differentially inhibit cell growth and downregulate the expression of matrix metalloproteinase-2 (MMP-2) at nontoxic concentrations.",

keywords = "Abyssinones, hydrogen-bonding catalysis, MMP-2 expression, prostate cancer",

author = "Farmer, \{Rebecca L.\} and Biddle, \{Margaret M.\} and Nibbs, \{Antoinette E.\} and Xiaoke Huang and Bergan, \{Raymond C.\} and Scheidt, \{Karl A.\}",

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doi = "10.1021/ml100110x",

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T1 - Concise syntheses of the abyssinones and discovery of new inhibitors of prostate cancer and MMP-2 expression

AU - Farmer, Rebecca L.

AU - Biddle, Margaret M.

AU - Nibbs, Antoinette E.

AU - Huang, Xiaoke

AU - Bergan, Raymond C.

AU - Scheidt, Karl A.

PY - 2010/11/11

Y1 - 2010/11/11

N2 - The first asymmetric syntheses of four members of the abyssinone class of natural products (I, II, III, and IV 4′-OMe) via quinine- or quinidine-derived thiourea-catalyzed intramolecular conjugate additions of β-keto ester alkylidenes are reported. This concise strategy delivers all four natural products and their corresponding antipodes. A preliminary evaluation of all of these small molecules against a metastatic human prostate cancer cell line has identified that these compounds selectively and differentially inhibit cell growth and downregulate the expression of matrix metalloproteinase-2 (MMP-2) at nontoxic concentrations.

AB - The first asymmetric syntheses of four members of the abyssinone class of natural products (I, II, III, and IV 4′-OMe) via quinine- or quinidine-derived thiourea-catalyzed intramolecular conjugate additions of β-keto ester alkylidenes are reported. This concise strategy delivers all four natural products and their corresponding antipodes. A preliminary evaluation of all of these small molecules against a metastatic human prostate cancer cell line has identified that these compounds selectively and differentially inhibit cell growth and downregulate the expression of matrix metalloproteinase-2 (MMP-2) at nontoxic concentrations.

KW - Abyssinones

KW - hydrogen-bonding catalysis

KW - MMP-2 expression

KW - prostate cancer

UR - https://www.scopus.com/pages/publications/78649305056

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DO - 10.1021/ml100110x

M3 - Article

AN - SCOPUS:78649305056

SN - 1948-5875

VL - 1

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JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 8

ER -

Concise syntheses of the abyssinones and discovery of new inhibitors of prostate cancer and MMP-2 expression

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Keywords

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