Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists

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

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Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists. / Mohsen, Amal M Y; Mandour, Yasmine M; Sarukhanyan, Edita; Breitinger, Ulrike; Villmann, Carmen; Banoub, Maha M; Breitinger, Hans-Georg; Dandekar, Thomas; Holzgrabe, Ulrike; Sotriffer, Christoph; Jensen, Anders A; Zlotos, Darius P.

In: Journal of Natural Products, Vol. 79, No. 12, 14.12.2016, p. 2997–3005.

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

Harvard

Mohsen, AMY, Mandour, YM, Sarukhanyan, E, Breitinger, U, Villmann, C, Banoub, MM, Breitinger, H-G, Dandekar, T, Holzgrabe, U, Sotriffer, C, Jensen, AA & Zlotos, DP 2016, 'Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists', Journal of Natural Products, vol. 79, no. 12, pp. 2997–3005. https://doi.org/10.1021/acs.jnatprod.6b00479

APA

Mohsen, A. M. Y., Mandour, Y. M., Sarukhanyan, E., Breitinger, U., Villmann, C., Banoub, M. M., Breitinger, H-G., Dandekar, T., Holzgrabe, U., Sotriffer, C., Jensen, A. A., & Zlotos, D. P. (2016). Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists. Journal of Natural Products, 79(12), 2997–3005. https://doi.org/10.1021/acs.jnatprod.6b00479

Vancouver

Mohsen AMY, Mandour YM, Sarukhanyan E, Breitinger U, Villmann C, Banoub MM et al. Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists. Journal of Natural Products. 2016 Dec 14;79(12):2997–3005. https://doi.org/10.1021/acs.jnatprod.6b00479

Author

Mohsen, Amal M Y ; Mandour, Yasmine M ; Sarukhanyan, Edita ; Breitinger, Ulrike ; Villmann, Carmen ; Banoub, Maha M ; Breitinger, Hans-Georg ; Dandekar, Thomas ; Holzgrabe, Ulrike ; Sotriffer, Christoph ; Jensen, Anders A ; Zlotos, Darius P. / Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists. In: Journal of Natural Products. 2016 ; Vol. 79, No. 12. pp. 2997–3005.

Bibtex

@article{9c5a18ed24894ac0a2054c13a311b145,
title = "Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists",
abstract = "A series of (E)-11-isonitrosostrychnine oxime ethers, 2-aminostrychnine, (strychnine-2-yl)propionamide, 18-oxostrychnine, and N-propylstrychnine bromide were synthesized and evaluated pharmacologically at human α1 and α1β glycine receptors in a functional fluorescence-based and a whole-cell patch-clamp assay and in [(3)H]strychnine binding studies. 2-Aminostrychnine and the methyl, allyl, and propargyl oxime ethers were the most potent α1 and α1β antagonists in the series, displaying IC50 values similar to those of strychnine at the two receptors. Docking experiments to the strychnine binding site of the crystal structure of the α3 glycine receptor indicated the same orientation of the strychnine core for all analogues. For the most potent oxime ethers, the ether substituent was accommodated in a lipophilic receptor binding pocket. The findings identify the oxime hydroxy group as a suitable attachment point for linking two strychnine pharmacophores by a polymethylene spacer and are, therefore, important for the design of bivalent ligands targeting glycine receptors.",
author = "Mohsen, {Amal M Y} and Mandour, {Yasmine M} and Edita Sarukhanyan and Ulrike Breitinger and Carmen Villmann and Banoub, {Maha M} and Hans-Georg Breitinger and Thomas Dandekar and Ulrike Holzgrabe and Christoph Sotriffer and Jensen, {Anders A} and Zlotos, {Darius P}",
year = "2016",
month = dec,
day = "14",
doi = "10.1021/acs.jnatprod.6b00479",
language = "English",
volume = "79",
pages = "2997–3005",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "12",

}

RIS

TY - JOUR

T1 - Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists

AU - Mohsen, Amal M Y

AU - Mandour, Yasmine M

AU - Sarukhanyan, Edita

AU - Breitinger, Ulrike

AU - Villmann, Carmen

AU - Banoub, Maha M

AU - Breitinger, Hans-Georg

AU - Dandekar, Thomas

AU - Holzgrabe, Ulrike

AU - Sotriffer, Christoph

AU - Jensen, Anders A

AU - Zlotos, Darius P

PY - 2016/12/14

Y1 - 2016/12/14

N2 - A series of (E)-11-isonitrosostrychnine oxime ethers, 2-aminostrychnine, (strychnine-2-yl)propionamide, 18-oxostrychnine, and N-propylstrychnine bromide were synthesized and evaluated pharmacologically at human α1 and α1β glycine receptors in a functional fluorescence-based and a whole-cell patch-clamp assay and in [(3)H]strychnine binding studies. 2-Aminostrychnine and the methyl, allyl, and propargyl oxime ethers were the most potent α1 and α1β antagonists in the series, displaying IC50 values similar to those of strychnine at the two receptors. Docking experiments to the strychnine binding site of the crystal structure of the α3 glycine receptor indicated the same orientation of the strychnine core for all analogues. For the most potent oxime ethers, the ether substituent was accommodated in a lipophilic receptor binding pocket. The findings identify the oxime hydroxy group as a suitable attachment point for linking two strychnine pharmacophores by a polymethylene spacer and are, therefore, important for the design of bivalent ligands targeting glycine receptors.

AB - A series of (E)-11-isonitrosostrychnine oxime ethers, 2-aminostrychnine, (strychnine-2-yl)propionamide, 18-oxostrychnine, and N-propylstrychnine bromide were synthesized and evaluated pharmacologically at human α1 and α1β glycine receptors in a functional fluorescence-based and a whole-cell patch-clamp assay and in [(3)H]strychnine binding studies. 2-Aminostrychnine and the methyl, allyl, and propargyl oxime ethers were the most potent α1 and α1β antagonists in the series, displaying IC50 values similar to those of strychnine at the two receptors. Docking experiments to the strychnine binding site of the crystal structure of the α3 glycine receptor indicated the same orientation of the strychnine core for all analogues. For the most potent oxime ethers, the ether substituent was accommodated in a lipophilic receptor binding pocket. The findings identify the oxime hydroxy group as a suitable attachment point for linking two strychnine pharmacophores by a polymethylene spacer and are, therefore, important for the design of bivalent ligands targeting glycine receptors.

U2 - 10.1021/acs.jnatprod.6b00479

DO - 10.1021/acs.jnatprod.6b00479

M3 - Journal article

C2 - 27966945

VL - 79

SP - 2997

EP - 3005

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 12

ER -

ID: 170157353