Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor.
Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor.
复制标题
通过TRPA1受体脱敏合成白藜芦醇衍生物作为新型镇痛药物。
DOI：
10.1016/j.bmcl.2017.05.025
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Dai Y.
中科院分区：
文献类型：
--
作者：
Nakao S;Mabuchi M;Wang S;Kogure Y;Shimizu T;Noguchi K;Tanaka A;Dai Y.
设计、合成了一系列31个白藜芦醇衍生物，并评价了其对TRPA 1通道的激活和抑制作用。大多数作为TRPA1通道的激活剂和脱敏剂，如白藜芦醇或异硫氰酸烯丙酯（AITC）。Compound4z（HUHS 029）的抑制活性高于白藜芦醇，IC 50值为16.1 μM。在表达TRPA1的HEK293细胞中，以及在大鼠背根神经节神经元中，通过全细胞膜片钳记录，证实了4zon TRPA1的活性。此外，4z预处理对体内AITC诱发的TRPA1相关疼痛行为表现出镇痛作用。
A series of 31 resveratrol derivatives was designed, synthesized and evaluated for activation and inhibition of the TRPA1 channel. Most acted as activators and desensitizers of TRPA1 channels like resveratrol or allyl isothiocyanate (AITC). Compound4z(HUHS029) exhibited higher inhibitory activity than resveratrol with an IC50value of 16.1 μM. The activity of4zon TRPA1 was confirmed in TRPA1-expressing HEK293 cells, as well as in rat dorsal root ganglia neurons by a whole cell patch clamp recording. Furthermore, pretreatment with4zexhibited an analgesic effect on AITC-evoked TRPA1-related pain behavior in vivo.