Criterio computacional para la obtención de compuestos análogos a anandamida

Abstract

Analogous compounds to anandamide derived from arachidonic acid and ethanolamine, previously proposed (1) as an alternative for the treatment of Parkinson's, which do not lose their functionality or generate adverse effects, and whose biological activity had not been evaluated experimentally or computationally were the object of this study. Its activity was determined as potential CB1 receptor antagonists (pdb: 5TGZ) by means of molecular docking. Subsequently, the viability of the synthesis routes was studied using the DFT Functional Theory (DFT). It was evidenced that all the ethanolamine derivatives have a behavior potentially antagonistic. In contrast, for the arachidonic acid derivatives, it was determined that only six of the thirteen proposed ligands have a biological activity potential. This was characterized for both derivatives by its position in the long channel of the receptor, far from the N-terminal and Extracellular II loops. Substrates 9H-carbazole, 1,2,3,4-tetrahydroisoquinoline-5,6-diol, 3-nitrobenzoic acid and 4-nitrobenzoic acid, were found to be viable as starting reagents for the synthesis of four potential antagonists on the CB1 receptor.