Nesterkina Mariia, Kravchenko Iryna
Department of Pharmaceutical Chemistry, I.I. Mechnikov Odessa National University, Odessa 65026, Ukraine.
Department of Organic and Pharmaceutical Technology, Odessa National Polytechnic University, Odessa 65044, Ukraine.
Pharmaceuticals (Basel). 2017 May 18;10(2):47. doi: 10.3390/ph10020047.
Esters based on mono- and bicyclic terpenoids with glycine have been synthesized via Steglich esterification and characterized by ¹H-NMR, IR, and mass spectral studies. Their analgesic and anti-inflammatory activities were investigated after transdermal delivery on models of formalin, capsaicin, and AITC-induced pain, respectively. Glycine esters of menthol and borneol exhibited higher antinociceptive action, whereas eugenol derivative significantly suppressed the development of the inflammatory process. The mechanism of competitive binding between terpenoid esters and TRPA1/TRPV1 agonists was proposed explaining significant analgesic effect of synthesized derivatives. For an explanation of high anti-inflammatory activity, competitive inhibition between terpenoid esters and AITC for binding sites of the TRPA1 ion channel has been suggested.
基于单环和双环萜类与甘氨酸的酯类化合物已通过施陶丁格酯化反应合成，并通过¹H-NMR、红外光谱和质谱研究进行了表征。分别在福尔马林、辣椒素和异硫氰酸烯丙酯诱导的疼痛模型上进行透皮给药后，研究了它们的镇痛和抗炎活性。薄荷醇和冰片的甘氨酸酯表现出更高的抗伤害感受作用，而丁香酚衍生物显著抑制了炎症过程的发展。提出了萜类酯与TRPA1/TRPV1激动剂之间的竞争性结合机制，以解释合成衍生物的显著镇痛作用。为了解释高抗炎活性，有人提出萜类酯与异硫氰酸烯丙酯在TRPA1离子通道结合位点上的竞争性抑制作用。
