Laboratory of Computational Systems Biology, School of Sciences - Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, Porto Alegre-RS 90619-900, Brazil.
Curr Med Chem. 2020;27(28):4741-4749. doi: 10.2174/0929867326666190906155339.
Cannabinoid receptor 1 has its crystallographic structure available in complex with agonists and inverse agonists, which paved the way to establish an understanding of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities and is widely used in some countries. Recently some evidence of a dipyrone metabolite acting over the Cannabinoid Receptor 1has been shown.
Our goal here is to explore the dipyrone metabolite 4-aminoantipyrine as a Cannabinoid Receptor 1 agonist, reviewing dipyrone characteristics, and investigating the structural basis for its interaction with the Cannabinoid Receptor 1.
We reviewed here recent functional studies related to the dipyrone metabolite focusing on its action as a Cannabinoid Receptor 1 agonist. We also analyzed protein-ligand interactions for this complex obtained through docking simulations against the crystallographic structure of the Cannabinoid Receptor 1.
Analysis of the crystallographic structure and docking simulations revealed that most of the interactions present in the docked pose were also present in the crystallographic structure of Cannabinoid Receptor 1 and agonist.
Analysis of the complex of 4-aminoantipyrine and Cannabinoid Receptor 1 revealed the pivotal role played by residues Phe 170, Phe 174, Phe 177, Phe 189, Leu 193, Val 196, and Phe 379, besides the conserved hydrogen bond at Ser 383. The mechanistic analysis and the present computational study suggest that the dipyrone metabolite 4-aminoantipyrine interacts with the Cannabinoid Receptor 1.
大麻素受体 1 与其激动剂和反向激动剂的晶体结构已经确定，这为理解与配体相互作用的结构基础铺平了道路。双氯芬酸是一种具有镇痛作用的前药，在一些国家被广泛使用。最近有证据表明双氯芬酸的一种代谢物作用于大麻素受体 1。
我们的目标是探索双氯芬酸的代谢物 4-氨基安替比林作为大麻素受体 1 的激动剂，回顾双氯芬酸的特性，并研究其与大麻素受体 1 相互作用的结构基础。
我们在这里回顾了最近与双氯芬酸代谢物相关的功能研究，重点关注其作为大麻素受体 1 激动剂的作用。我们还分析了通过对接模拟获得的该复合物与大麻素受体 1 的晶体结构之间的蛋白质-配体相互作用。
晶体结构分析和对接模拟表明，对接构象中存在的大多数相互作用也存在于大麻素受体 1 和激动剂的晶体结构中。
对 4-氨基安替比林和大麻素受体 1 复合物的分析揭示了残基 Phe 170、Phe 174、Phe 177、Phe 189、Leu 193、Val 196 和 Phe 379 以及 Ser 383 处保守氢键所起的关键作用。机制分析和本计算研究表明，双氯芬酸的代谢物 4-氨基安替比林与大麻素受体 1 相互作用。
