TRPA1 Inhibition Effects by 3-Phenylcoumarin Derivatives

Carita Sallomy; Paul Awolade; Minna Rahnasto-Rilla; Mari Hämäläinen; Liisa P. Nousiainen; Niklas G. Johansson; Sanna Hiltunen; Petri Turhanen; Eeva Moilanen; Maija Lahtela-Kakkonen; Juri M. Timonen

doi:10.1021/acsmedchemlett.4c00072

TRPA1 Inhibition Effects by 3-Phenylcoumarin Derivatives

Carita Sallomy, Paul Awolade, Minna Rahnasto-Rilla, Mari Hämäläinen, Liisa P. Nousiainen, Niklas G. Johansson, Sanna Hiltunen, Petri Turhanen, Eeva Moilanen, Maija Lahtela-Kakkonen, Juri M. Timonen

Tutkimustuotos: Artikkelijulkaisu › Artikkeli › Tieteellinen › vertaisarvioitu

Abstrakti

Transient receptor potential ankyrin 1 (TRPA1) protein plays an important role in the inflammatory response, and it has been associated with different pain conditions and pain-related diseases, making TRPA1 a valid target for painkillers. In this study, we identified potential TRPA1 inhibitors and located their binding sites utilizing computer-aided drug design (CADD) techniques. The designed 3-phenylcoumarin-based TRPA1 inhibitors were successfully synthesized using a microwave assisted synthetic strategy. 3-(3-Bromophenyl)-7-acetoxycoumarin (5), 7-hydroxy-3-(3-hydroxyphenyl)coumarin (12) and 3-(3-hydroxyphenyl)coumarin (23) all showed inhibitory activity toward TRPA1 in vitro. Compound 5 also decreased the size and formation of breast cancer cells. Hence, targeting TRPA1 may represent a promising alternative for the treatment of pain and inflammation.

Alkuperäiskieli	englanti
Lehti	ACS Medicinal Chemistry Letters
ISSN	1948-5875
DOI - pysyväislinkit	https://doi.org/10.1021/acsmedchemlett.4c00072
Tila	Julkaistu - 2 heinäk. 2024
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Lisätietoja

Publisher Copyright:
© 2024 American Chemical Society.

Tieteenalat

116 Kemia

Pääsy asiakirjaan

10.1021/acsmedchemlett.4c00072Lisenssi: CC BY

sallomy-et-al-2024-trpa1-inhibition-effects-by-3-phenylcoumarin-derivativesLopullinen julkaistu versio, 3,66 MBLisenssi: CC BY

Siteeraa tätä

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title = "TRPA1 Inhibition Effects by 3-Phenylcoumarin Derivatives",

abstract = "Transient receptor potential ankyrin 1 (TRPA1) protein plays an important role in the inflammatory response, and it has been associated with different pain conditions and pain-related diseases, making TRPA1 a valid target for painkillers. In this study, we identified potential TRPA1 inhibitors and located their binding sites utilizing computer-aided drug design (CADD) techniques. The designed 3-phenylcoumarin-based TRPA1 inhibitors were successfully synthesized using a microwave assisted synthetic strategy. 3-(3-Bromophenyl)-7-acetoxycoumarin (5), 7-hydroxy-3-(3-hydroxyphenyl)coumarin (12) and 3-(3-hydroxyphenyl)coumarin (23) all showed inhibitory activity toward TRPA1 in vitro. Compound 5 also decreased the size and formation of breast cancer cells. Hence, targeting TRPA1 may represent a promising alternative for the treatment of pain and inflammation.",

keywords = "computational modeling, neuropathic pain, phenylcoumarin, TRPA1, 116 Chemical sciences",

author = "Carita Sallomy and Paul Awolade and Minna Rahnasto-Rilla and Mari H{\"a}m{\"a}l{\"a}inen and Nousiainen, {Liisa P.} and Johansson, {Niklas G.} and Sanna Hiltunen and Petri Turhanen and Eeva Moilanen and Maija Lahtela-Kakkonen and Timonen, {Juri M.}",

note = "Publisher Copyright: {\textcopyright} 2024 American Chemical Society.",

year = "2024",

month = jul,

day = "2",

doi = "10.1021/acsmedchemlett.4c00072",

language = "English",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

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TY - JOUR

T1 - TRPA1 Inhibition Effects by 3-Phenylcoumarin Derivatives

AU - Sallomy, Carita

AU - Awolade, Paul

AU - Rahnasto-Rilla, Minna

AU - Hämäläinen, Mari

AU - Nousiainen, Liisa P.

AU - Johansson, Niklas G.

AU - Hiltunen, Sanna

AU - Turhanen, Petri

AU - Moilanen, Eeva

AU - Lahtela-Kakkonen, Maija

AU - Timonen, Juri M.

PY - 2024/7/2

Y1 - 2024/7/2

N2 - Transient receptor potential ankyrin 1 (TRPA1) protein plays an important role in the inflammatory response, and it has been associated with different pain conditions and pain-related diseases, making TRPA1 a valid target for painkillers. In this study, we identified potential TRPA1 inhibitors and located their binding sites utilizing computer-aided drug design (CADD) techniques. The designed 3-phenylcoumarin-based TRPA1 inhibitors were successfully synthesized using a microwave assisted synthetic strategy. 3-(3-Bromophenyl)-7-acetoxycoumarin (5), 7-hydroxy-3-(3-hydroxyphenyl)coumarin (12) and 3-(3-hydroxyphenyl)coumarin (23) all showed inhibitory activity toward TRPA1 in vitro. Compound 5 also decreased the size and formation of breast cancer cells. Hence, targeting TRPA1 may represent a promising alternative for the treatment of pain and inflammation.

AB - Transient receptor potential ankyrin 1 (TRPA1) protein plays an important role in the inflammatory response, and it has been associated with different pain conditions and pain-related diseases, making TRPA1 a valid target for painkillers. In this study, we identified potential TRPA1 inhibitors and located their binding sites utilizing computer-aided drug design (CADD) techniques. The designed 3-phenylcoumarin-based TRPA1 inhibitors were successfully synthesized using a microwave assisted synthetic strategy. 3-(3-Bromophenyl)-7-acetoxycoumarin (5), 7-hydroxy-3-(3-hydroxyphenyl)coumarin (12) and 3-(3-hydroxyphenyl)coumarin (23) all showed inhibitory activity toward TRPA1 in vitro. Compound 5 also decreased the size and formation of breast cancer cells. Hence, targeting TRPA1 may represent a promising alternative for the treatment of pain and inflammation.

KW - computational modeling

KW - neuropathic pain

KW - phenylcoumarin

KW - TRPA1

KW - 116 Chemical sciences

U2 - 10.1021/acsmedchemlett.4c00072

DO - 10.1021/acsmedchemlett.4c00072

M3 - Article

SN - 1948-5875

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

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