Sallomy Carita, Awolade Paul, Rahnasto-Rilla Minna, Hämäläinen Mari, Nousiainen Liisa P, Johansson Niklas G, Hiltunen Sanna, Turhanen Petri, Moilanen Eeva, Lahtela-Kakkonen Maija, Timonen Juri M
School of Pharmacy, University of Eastern Finland, Kuopio 70211, Finland.
School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban 4041, South Africa.
ACS Med Chem Lett. 2024 Jul 2;15(8):1221-1226. doi: 10.1021/acsmedchemlett.4c00072. eCollection 2024 Aug 8.
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 (), 7-hydroxy-3-(3-hydroxyphenyl)coumarin () and 3-(3-hydroxyphenyl)coumarin () all showed inhibitory activity toward TRPA1 . Compound 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.
瞬时受体电位锚蛋白1（TRPA1）蛋白在炎症反应中起重要作用，并且它与不同的疼痛状况和疼痛相关疾病有关，这使得TRPA1成为止痛药的有效靶点。在本研究中，我们利用计算机辅助药物设计（CADD）技术鉴定了潜在的TRPA1抑制剂并确定了它们的结合位点。使用微波辅助合成策略成功合成了设计的基于3-苯基香豆素的TRPA1抑制剂。3-（3-溴苯基）-7-乙酰氧基香豆素（）、7-羟基-3-（3-羟基苯基）香豆素（）和3-（3-羟基苯基）香豆素（）均对TRPA1表现出抑制活性。化合物还减小了乳腺癌细胞的大小并抑制了其形成。因此，靶向TRPA1可能是治疗疼痛和炎症的一种有前景的替代方法。
