The neuronal calcium ion channel activity of constrained analogues of MONIRO-1

Fernanda C. Cardoso; Marie-Adeline Marliac; Chloe Geoffroy; Matthieu Schmit; Anjie Bispat; Richard J. Lewis; Kellie L. Tuck; Peter J. Duggan

doi:10.1016/j.bmc.2020.115655

The neuronal calcium ion channel activity of constrained analogues of MONIRO-1

Fernanda C. Cardoso
, Marie-Adeline Marliac
, Chloe Geoffroy
, Matthieu Schmit
, Anjie Bispat
, Richard J. Lewis
, Kellie L. Tuck
, Peter J. Duggan

College of Science and Engineering

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

9 Citations (Scopus)

Abstract

Structural modifications of the neuronal calcium channel blocker MONIRO-1, including constraining the phenoxyaniline portion of the molecule and replacing the guanidinium functionality with tertiary amines, led to compounds with significantly improved affinities for the endogenously expressed Ca_V2.2 channel in the SH-SY5Y neuroblastoma cell line. These analogues also showed promising activity towards the Ca_V3.2 channel, recombinantly expressed in HEK293T cells. Both of these ion channels have received attention as likely targets for the treatment of neuropathic pain. The dibenzoazepine and dihydrobenzodiazepine derivatives prepared in this study show an encouraging combination of neuronal calcium ion channel inhibitory potency, plasma stability and potential to cross the blood–brain-barrier.

Original language	English
Article number	115655
Number of pages	10
Journal	Bioorganic & Medicinal Chemistry
Volume	28
Issue number	18
DOIs	https://doi.org/10.1016/j.bmc.2020.115655
Publication status	Published - 15 Sept 2020

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Benzodiazepine
Ca2.2
Ca3.2
N-type calcium channel
Pain
T-type calcium channel

Access to Document

10.1016/j.bmc.2020.115655Licence: In Copyright

Cite this

@article{822c3176fff14884852a005d81ff28df,

title = "The neuronal calcium ion channel activity of constrained analogues of MONIRO-1",

abstract = "Structural modifications of the neuronal calcium channel blocker MONIRO-1, including constraining the phenoxyaniline portion of the molecule and replacing the guanidinium functionality with tertiary amines, led to compounds with significantly improved affinities for the endogenously expressed CaV2.2 channel in the SH-SY5Y neuroblastoma cell line. These analogues also showed promising activity towards the CaV3.2 channel, recombinantly expressed in HEK293T cells. Both of these ion channels have received attention as likely targets for the treatment of neuropathic pain. The dibenzoazepine and dihydrobenzodiazepine derivatives prepared in this study show an encouraging combination of neuronal calcium ion channel inhibitory potency, plasma stability and potential to cross the blood–brain-barrier.",

keywords = "Benzodiazepine, Ca2.2, Ca3.2, N-type calcium channel, Pain, T-type calcium channel",

author = "Cardoso, \{Fernanda C.\} and Marie-Adeline Marliac and Chloe Geoffroy and Matthieu Schmit and Anjie Bispat and Lewis, \{Richard J.\} and Tuck, \{Kellie L.\} and Duggan, \{Peter J.\}",

year = "2020",

month = sep,

day = "15",

doi = "10.1016/j.bmc.2020.115655",

language = "English",

volume = "28",

journal = "Bioorganic \& Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "18",

}

TY - JOUR

T1 - The neuronal calcium ion channel activity of constrained analogues of MONIRO-1

AU - Cardoso, Fernanda C.

AU - Marliac, Marie-Adeline

AU - Geoffroy, Chloe

AU - Schmit, Matthieu

AU - Bispat, Anjie

AU - Lewis, Richard J.

AU - Tuck, Kellie L.

AU - Duggan, Peter J.

PY - 2020/9/15

Y1 - 2020/9/15

N2 - Structural modifications of the neuronal calcium channel blocker MONIRO-1, including constraining the phenoxyaniline portion of the molecule and replacing the guanidinium functionality with tertiary amines, led to compounds with significantly improved affinities for the endogenously expressed CaV2.2 channel in the SH-SY5Y neuroblastoma cell line. These analogues also showed promising activity towards the CaV3.2 channel, recombinantly expressed in HEK293T cells. Both of these ion channels have received attention as likely targets for the treatment of neuropathic pain. The dibenzoazepine and dihydrobenzodiazepine derivatives prepared in this study show an encouraging combination of neuronal calcium ion channel inhibitory potency, plasma stability and potential to cross the blood–brain-barrier.

AB - Structural modifications of the neuronal calcium channel blocker MONIRO-1, including constraining the phenoxyaniline portion of the molecule and replacing the guanidinium functionality with tertiary amines, led to compounds with significantly improved affinities for the endogenously expressed CaV2.2 channel in the SH-SY5Y neuroblastoma cell line. These analogues also showed promising activity towards the CaV3.2 channel, recombinantly expressed in HEK293T cells. Both of these ion channels have received attention as likely targets for the treatment of neuropathic pain. The dibenzoazepine and dihydrobenzodiazepine derivatives prepared in this study show an encouraging combination of neuronal calcium ion channel inhibitory potency, plasma stability and potential to cross the blood–brain-barrier.

KW - Benzodiazepine

KW - Ca2.2

KW - Ca3.2

KW - N-type calcium channel

KW - Pain

KW - T-type calcium channel

UR - https://www.scopus.com/pages/publications/85088423698

UR - http://purl.org/au-research/grants/NHMRC/1072113

UR - http://purl.org/au-research/grants/NHMRC/1119056

U2 - 10.1016/j.bmc.2020.115655

DO - 10.1016/j.bmc.2020.115655

M3 - Article

C2 - 32828422

AN - SCOPUS:85088423698

SN - 0968-0896

VL - 28

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 18

M1 - 115655

ER -

The neuronal calcium ion channel activity of constrained analogues of MONIRO-1

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this