Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation

Carmela Napolitano; Alessandro Natoni; Corrado Santocanale; Lasse Evensen; James B. Lorens; Paul V. Murphy

doi:10.1016/j.bmcl.2010.12.100

Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation

Carmela Napolitano
, Alessandro Natoni
, Corrado Santocanale
, Lasse Evensen
, James B. Lorens
, Paul V. Murphy

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

10 Citations (Scopus)

Abstract

The synthesis of a small library of resorcylic acid lactones and evaluation of their biological properties as kinase inhibitors is described. Within the series E-enones were found more active than corresponding Z-enones as inhibitors of a subset of kinases containing a conserved cysteine. Replacement of the enone moiety with a β-haloketone group led to compounds with an interesting kinase selectivity profile and also antiproliferative activity against Jurkat cells. An E-enone derivative also showed activity against capillary tube formation based on a co-culture of primary human umbilical cord endothelial cells (HUVECs) and vascular smooth muscle cells (vSMCs).

Original language	English
Pages (from-to)	1167-1170
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2010.12.100
Publication status	Published - 15 Feb 2011

Keywords

Kinase inhibitors
Photoisomerization
Resorcylic acid lactones
Tumor growth

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2010.12.100

Cite this

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title = "Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation",

abstract = "The synthesis of a small library of resorcylic acid lactones and evaluation of their biological properties as kinase inhibitors is described. Within the series E-enones were found more active than corresponding Z-enones as inhibitors of a subset of kinases containing a conserved cysteine. Replacement of the enone moiety with a β-haloketone group led to compounds with an interesting kinase selectivity profile and also antiproliferative activity against Jurkat cells. An E-enone derivative also showed activity against capillary tube formation based on a co-culture of primary human umbilical cord endothelial cells (HUVECs) and vascular smooth muscle cells (vSMCs).",

keywords = "Kinase inhibitors, Photoisomerization, Resorcylic acid lactones, Tumor growth",

author = "Carmela Napolitano and Alessandro Natoni and Corrado Santocanale and Lasse Evensen and Lorens, \{James B.\} and Murphy, \{Paul V.\}",

year = "2011",

month = feb,

day = "15",

doi = "10.1016/j.bmcl.2010.12.100",

language = "English",

volume = "21",

pages = "1167--1170",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "4",

}

Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation. / Napolitano, Carmela; Natoni, Alessandro; Santocanale, Corrado et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 4, 15.02.2011, p. 1167-1170.

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

TY - JOUR

T1 - Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation

AU - Napolitano, Carmela

AU - Natoni, Alessandro

AU - Santocanale, Corrado

AU - Evensen, Lasse

AU - Lorens, James B.

AU - Murphy, Paul V.

PY - 2011/2/15

Y1 - 2011/2/15

N2 - The synthesis of a small library of resorcylic acid lactones and evaluation of their biological properties as kinase inhibitors is described. Within the series E-enones were found more active than corresponding Z-enones as inhibitors of a subset of kinases containing a conserved cysteine. Replacement of the enone moiety with a β-haloketone group led to compounds with an interesting kinase selectivity profile and also antiproliferative activity against Jurkat cells. An E-enone derivative also showed activity against capillary tube formation based on a co-culture of primary human umbilical cord endothelial cells (HUVECs) and vascular smooth muscle cells (vSMCs).

AB - The synthesis of a small library of resorcylic acid lactones and evaluation of their biological properties as kinase inhibitors is described. Within the series E-enones were found more active than corresponding Z-enones as inhibitors of a subset of kinases containing a conserved cysteine. Replacement of the enone moiety with a β-haloketone group led to compounds with an interesting kinase selectivity profile and also antiproliferative activity against Jurkat cells. An E-enone derivative also showed activity against capillary tube formation based on a co-culture of primary human umbilical cord endothelial cells (HUVECs) and vascular smooth muscle cells (vSMCs).

KW - Kinase inhibitors

KW - Photoisomerization

KW - Resorcylic acid lactones

KW - Tumor growth

UR - https://www.scopus.com/pages/publications/79851507873

U2 - 10.1016/j.bmcl.2010.12.100

DO - 10.1016/j.bmcl.2010.12.100

M3 - Article

SN - 0960-894X

VL - 21

SP - 1167

EP - 1170

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation

Abstract

Keywords

UN SDGs

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