Strategies for improving the solubility and metabolic stability of griseofulvin analogues

Asger Bjørn Petersen; G. Konotop; N. H. M. Hanafiah; Peter Hammershøj; M. S. Raab; A. Kraemer; Mads Hartvig Clausen

doi:10.1016/j.ejmech.2016.03.071

Strategies for improving the solubility and metabolic stability of griseofulvin analogues

Asger Bjørn Petersen, G. Konotop, N. H. M. Hanafiah, Peter Hammershøj, M. S. Raab, A. Kraemer, Mads Hartvig Clausen

Department of Chemistry

German Cancer Research Center

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

We report two types of modifications to the natural product griseofulvin as strategies to improve solubility and metabolic stability: the conversion of aryl methyl ethers into aryl difluoromethyl ethers at metabolic hotspots and the conversion of the C-ring ketone into polar oximes. The syntheses of the analogues are described together with their solubility, metabolic half-life in vitro and antiproliferative effect in two cancer cell lines. We conclude that on balance, the formation of polar oximes is the most promising strategy for improving the properties of the analogues.

Original language	English
Journal	European Journal of Medicinal Chemistry
Volume	116
Pages (from-to)	210-215
Number of pages	6
ISSN	0223-5234
DOIs	https://doi.org/10.1016/j.ejmech.2016.03.071
Publication status	Published - 2016

Keywords

Griseofulvin analogues
Anticancer
Synthesis
Antifungal
Metabolic stability

UN SDGs

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

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10.1016/j.ejmech.2016.03.071

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title = "Strategies for improving the solubility and metabolic stability of griseofulvin analogues",

abstract = "We report two types of modifications to the natural product griseofulvin as strategies to improve solubility and metabolic stability: the conversion of aryl methyl ethers into aryl difluoromethyl ethers at metabolic hotspots and the conversion of the C-ring ketone into polar oximes. The syntheses of the analogues are described together with their solubility, metabolic half-life in vitro and antiproliferative effect in two cancer cell lines. We conclude that on balance, the formation of polar oximes is the most promising strategy for improving the properties of the analogues.",

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AU - Petersen, Asger Bjørn

AU - Konotop, G.

AU - Hanafiah, N. H. M.

AU - Hammershøj, Peter

AU - Raab, M. S.

AU - Kraemer, A.

AU - Clausen, Mads Hartvig

PY - 2016

Y1 - 2016

N2 - We report two types of modifications to the natural product griseofulvin as strategies to improve solubility and metabolic stability: the conversion of aryl methyl ethers into aryl difluoromethyl ethers at metabolic hotspots and the conversion of the C-ring ketone into polar oximes. The syntheses of the analogues are described together with their solubility, metabolic half-life in vitro and antiproliferative effect in two cancer cell lines. We conclude that on balance, the formation of polar oximes is the most promising strategy for improving the properties of the analogues.

AB - We report two types of modifications to the natural product griseofulvin as strategies to improve solubility and metabolic stability: the conversion of aryl methyl ethers into aryl difluoromethyl ethers at metabolic hotspots and the conversion of the C-ring ketone into polar oximes. The syntheses of the analogues are described together with their solubility, metabolic half-life in vitro and antiproliferative effect in two cancer cell lines. We conclude that on balance, the formation of polar oximes is the most promising strategy for improving the properties of the analogues.

KW - Griseofulvin analogues

KW - Anticancer

KW - Synthesis

KW - Antifungal

KW - Metabolic stability

U2 - 10.1016/j.ejmech.2016.03.071

DO - 10.1016/j.ejmech.2016.03.071

M3 - Journal article

C2 - 27061984

SN - 0223-5234

VL - 116

SP - 210

EP - 215

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Strategies for improving the solubility and metabolic stability of griseofulvin analogues

Abstract

Keywords

UN SDGs

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