Steroidal derived acids as inhibitors of human Cdc25A protein phosphatase

Hairuo Peng; Wenge Xie; Deog Il Kim; Leon H. Zalkow; Garth Powis; Diane M. Otterness; Robert T. Abraham

doi:10.1016/S0968-0896(99)00284-9

Steroidal derived acids as inhibitors of human Cdc25A protein phosphatase

Hairuo Peng, Wenge Xie, Deog Il Kim, Leon H. Zalkow, Garth Powis, Diane M. Otterness, Robert T. Abraham

Experimental Therapeutics

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

16 Scopus citations

Abstract

A group of steroidal derived acids were synthesized and found to be human Cdc25A inhibitors. Their potency ranged from 1.1 to > 100 μM; the best ones compare very favorably with that of the novel cyano-containing 5,6-seco- cholesteryl acid 1 (IC₅₀ = 2.2 μM) reported by us recently (Peng, H.; Zalkow, L. H.; Abraham, R. T.; Powis, G. J. Med. Chem. 1998, 41, 4677). Structure-activity relationships of these compounds revealed that a hydrophobic cholesteryl side chain and a free carboxyl group are crucial for activity. The distance between these two pharmacophores is also important for the potency of these compounds. Several of the compounds showed selective growth inhibition effects in the NCI in vitro cancer cell line panel. (C) 2000 Elsevier Science Ltd.

Original language	English (US)
Pages (from-to)	299-306
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	8
Issue number	2
DOIs	https://doi.org/10.1016/S0968-0896(99)00284-9
State	Published - Feb 2000

Keywords

Antiproliferatives agents
Antitumor compds
Enzyme inhibitors
Steroids and sterols

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0968-0896(99)00284-9

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title = "Steroidal derived acids as inhibitors of human Cdc25A protein phosphatase",

abstract = "A group of steroidal derived acids were synthesized and found to be human Cdc25A inhibitors. Their potency ranged from 1.1 to > 100 μM; the best ones compare very favorably with that of the novel cyano-containing 5,6-seco- cholesteryl acid 1 (IC50 = 2.2 μM) reported by us recently (Peng, H.; Zalkow, L. H.; Abraham, R. T.; Powis, G. J. Med. Chem. 1998, 41, 4677). Structure-activity relationships of these compounds revealed that a hydrophobic cholesteryl side chain and a free carboxyl group are crucial for activity. The distance between these two pharmacophores is also important for the potency of these compounds. Several of the compounds showed selective growth inhibition effects in the NCI in vitro cancer cell line panel. (C) 2000 Elsevier Science Ltd.",

keywords = "Antiproliferatives agents, Antitumor compds, Enzyme inhibitors, Steroids and sterols",

author = "Hairuo Peng and Wenge Xie and Kim, {Deog Il} and Zalkow, {Leon H.} and Garth Powis and Otterness, {Diane M.} and Abraham, {Robert T.}",

note = "Funding Information: We gratefully acknowledge support of this research by the NCI/NIH (Grant 5U19 CA52995). We are grateful to Dr. Leslie T. Gelbaum, Mr. David E. Bostwick and Ms. Sarah J. Shealy for their assistance in obtaining high resolution NMR, mass spectra. ",

year = "2000",

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doi = "10.1016/S0968-0896(99)00284-9",

language = "English (US)",

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AU - Peng, Hairuo

AU - Xie, Wenge

AU - Kim, Deog Il

AU - Zalkow, Leon H.

AU - Powis, Garth

AU - Otterness, Diane M.

AU - Abraham, Robert T.

N1 - Funding Information: We gratefully acknowledge support of this research by the NCI/NIH (Grant 5U19 CA52995). We are grateful to Dr. Leslie T. Gelbaum, Mr. David E. Bostwick and Ms. Sarah J. Shealy for their assistance in obtaining high resolution NMR, mass spectra.

PY - 2000/2

Y1 - 2000/2

N2 - A group of steroidal derived acids were synthesized and found to be human Cdc25A inhibitors. Their potency ranged from 1.1 to > 100 μM; the best ones compare very favorably with that of the novel cyano-containing 5,6-seco- cholesteryl acid 1 (IC50 = 2.2 μM) reported by us recently (Peng, H.; Zalkow, L. H.; Abraham, R. T.; Powis, G. J. Med. Chem. 1998, 41, 4677). Structure-activity relationships of these compounds revealed that a hydrophobic cholesteryl side chain and a free carboxyl group are crucial for activity. The distance between these two pharmacophores is also important for the potency of these compounds. Several of the compounds showed selective growth inhibition effects in the NCI in vitro cancer cell line panel. (C) 2000 Elsevier Science Ltd.

AB - A group of steroidal derived acids were synthesized and found to be human Cdc25A inhibitors. Their potency ranged from 1.1 to > 100 μM; the best ones compare very favorably with that of the novel cyano-containing 5,6-seco- cholesteryl acid 1 (IC50 = 2.2 μM) reported by us recently (Peng, H.; Zalkow, L. H.; Abraham, R. T.; Powis, G. J. Med. Chem. 1998, 41, 4677). Structure-activity relationships of these compounds revealed that a hydrophobic cholesteryl side chain and a free carboxyl group are crucial for activity. The distance between these two pharmacophores is also important for the potency of these compounds. Several of the compounds showed selective growth inhibition effects in the NCI in vitro cancer cell line panel. (C) 2000 Elsevier Science Ltd.

KW - Antiproliferatives agents

KW - Antitumor compds

KW - Enzyme inhibitors

KW - Steroids and sterols

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ER -

Steroidal derived acids as inhibitors of human Cdc25A protein phosphatase

Abstract

Keywords

ASJC Scopus subject areas

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