11-Aminostrychnine and N-(Strychnine-11-yl)propionamide: Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors

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

Standard

11-Aminostrychnine and N-(Strychnine-11-yl)propionamide : Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors. / Zlotos, Darius P; Mohsen, Amal M Y; Mandour, Yasmine M; Marzouk, Mohamed A; Breitinger, Ulrike; Villmann, Carmen; Breitinger, Hans-Georg; Sotriffer, Christoph; Jensen, Anders A; Holzgrabe, Ulrike.

In: Journal of Natural Products, Vol. 82, 06.08.2019, p. 2332-2336.

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

Harvard

Zlotos, DP, Mohsen, AMY, Mandour, YM, Marzouk, MA, Breitinger, U, Villmann, C, Breitinger, H-G, Sotriffer, C, Jensen, AA & Holzgrabe, U 2019, '11-Aminostrychnine and N-(Strychnine-11-yl)propionamide: Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors', Journal of Natural Products, vol. 82, pp. 2332-2336. https://doi.org/10.1021/acs.jnatprod.9b00180

APA

Zlotos, D. P., Mohsen, A. M. Y., Mandour, Y. M., Marzouk, M. A., Breitinger, U., Villmann, C., Breitinger, H-G., Sotriffer, C., Jensen, A. A., & Holzgrabe, U. (2019). 11-Aminostrychnine and N-(Strychnine-11-yl)propionamide: Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors. Journal of Natural Products, 82, 2332-2336. https://doi.org/10.1021/acs.jnatprod.9b00180

Vancouver

Zlotos DP, Mohsen AMY, Mandour YM, Marzouk MA, Breitinger U, Villmann C et al. 11-Aminostrychnine and N-(Strychnine-11-yl)propionamide: Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors. Journal of Natural Products. 2019 Aug 6;82:2332-2336. https://doi.org/10.1021/acs.jnatprod.9b00180

Author

Zlotos, Darius P ; Mohsen, Amal M Y ; Mandour, Yasmine M ; Marzouk, Mohamed A ; Breitinger, Ulrike ; Villmann, Carmen ; Breitinger, Hans-Georg ; Sotriffer, Christoph ; Jensen, Anders A ; Holzgrabe, Ulrike. / 11-Aminostrychnine and N-(Strychnine-11-yl)propionamide : Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors. In: Journal of Natural Products. 2019 ; Vol. 82. pp. 2332-2336.

Bibtex

@article{ebe85280c08244adbaf410be0a2f8522,
title = "11-Aminostrychnine and N-(Strychnine-11-yl)propionamide: Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors",
abstract = "(11S)-11-Aminostrychnine (1) and N-[(11S)-strychnine-11-yl]propionamide (2) were synthesized and characterized as antagonists of homomeric α1 and heteromeric α1β glycine receptors in a functional fluorescence-based assay and a patch-clamp assay and in radioligand binding studies. The absolute configuration at C-11 of 1 was determined based on vicinal coupling constants and NOESY data. Docking experiments to the orthosteric binding site of the α3 glycine receptor showed a binding mode of compound 2 analogous to that of strychnine, explaining its high antagonistic potency. The findings identify the C-11 amide function of strychnine as a suitable linker group for the future development of dimeric strychnine analogues targeting glycine receptors. The findings extend the SAR of strychnine at glycine receptors.",
author = "Zlotos, {Darius P} and Mohsen, {Amal M Y} and Mandour, {Yasmine M} and Marzouk, {Mohamed A} and Ulrike Breitinger and Carmen Villmann and Hans-Georg Breitinger and Christoph Sotriffer and Jensen, {Anders A} and Ulrike Holzgrabe",
year = "2019",
month = aug,
day = "6",
doi = "10.1021/acs.jnatprod.9b00180",
language = "English",
volume = "82",
pages = "2332--2336",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - 11-Aminostrychnine and N-(Strychnine-11-yl)propionamide

T2 - Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors

AU - Zlotos, Darius P

AU - Mohsen, Amal M Y

AU - Mandour, Yasmine M

AU - Marzouk, Mohamed A

AU - Breitinger, Ulrike

AU - Villmann, Carmen

AU - Breitinger, Hans-Georg

AU - Sotriffer, Christoph

AU - Jensen, Anders A

AU - Holzgrabe, Ulrike

PY - 2019/8/6

Y1 - 2019/8/6

N2 - (11S)-11-Aminostrychnine (1) and N-[(11S)-strychnine-11-yl]propionamide (2) were synthesized and characterized as antagonists of homomeric α1 and heteromeric α1β glycine receptors in a functional fluorescence-based assay and a patch-clamp assay and in radioligand binding studies. The absolute configuration at C-11 of 1 was determined based on vicinal coupling constants and NOESY data. Docking experiments to the orthosteric binding site of the α3 glycine receptor showed a binding mode of compound 2 analogous to that of strychnine, explaining its high antagonistic potency. The findings identify the C-11 amide function of strychnine as a suitable linker group for the future development of dimeric strychnine analogues targeting glycine receptors. The findings extend the SAR of strychnine at glycine receptors.

AB - (11S)-11-Aminostrychnine (1) and N-[(11S)-strychnine-11-yl]propionamide (2) were synthesized and characterized as antagonists of homomeric α1 and heteromeric α1β glycine receptors in a functional fluorescence-based assay and a patch-clamp assay and in radioligand binding studies. The absolute configuration at C-11 of 1 was determined based on vicinal coupling constants and NOESY data. Docking experiments to the orthosteric binding site of the α3 glycine receptor showed a binding mode of compound 2 analogous to that of strychnine, explaining its high antagonistic potency. The findings identify the C-11 amide function of strychnine as a suitable linker group for the future development of dimeric strychnine analogues targeting glycine receptors. The findings extend the SAR of strychnine at glycine receptors.

U2 - 10.1021/acs.jnatprod.9b00180

DO - 10.1021/acs.jnatprod.9b00180

M3 - Journal article

C2 - 31385511

VL - 82

SP - 2332

EP - 2336

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

ER -

ID: 225718919