TRPA1 Inhibition Effects by 3-Phenylcoumarin Derivatives.

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.