Next Article in Journal
Updates on Aptamer Research
Next Article in Special Issue
Quantitative Structure–Activity Relationships for Structurally Diverse Chemotypes Having Anti-Trypanosoma cruzi Activity
Previous Article in Journal
The Effects of Proteasome Inhibitors on Telomerase Activity and Regulation in Multiple Myeloma Cells
Previous Article in Special Issue
Structure-Based Approach for the Prediction of Mu-opioid Binding Affinity of Unclassified Designer Fentanyl-Like Molecules
Open AccessArticle

Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) on a Series of Piperazine-Carboxamides Fatty Acid Amide Hydrolase (FAAH) Inhibitors as a Useful Tool for the Design of New Cannabinoid Ligands

1
Escuela de Quimica y Farmacia, Facultad de Medicina, Universidad Andres Bello, Quillota 980, Viña del Mar 2531015, Chile
2
Pharmacy Department, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Santiago 7820436, Chile
3
Departamento de Ciencias Farmacéuticas, Facultad de Ciencias, Universidad Católica del Norte, Avenida Angamos 0610, Antofagasta 1270709, Chile
4
Instituto de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Valparaíso 2360102, Chile
5
Centro de Investigación Farmacopea Chilena (CIFAR), Universidad de Valparaíso, Santa Marta 183, Valparaíso 2360134, Chile
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(10), 2510; https://doi.org/10.3390/ijms20102510
Received: 21 February 2019 / Revised: 27 April 2019 / Accepted: 7 May 2019 / Published: 21 May 2019
(This article belongs to the Special Issue QSAR and Chemoinformatics Tools for Modeling)
Fatty Acid Amide Hydrolase (FAAH) is one of the main enzymes responsible for endocannabinoid metabolism. Inhibition of FAAH increases endogenous levels of fatty acid ethanolamides such as anandamide (AEA) and thus consitutes an indirect strategy that can be used to modulate endocannabinoid tone. In the present work, we present a three-dimensional quantitative structure-activity relationships/comparative molecular similarity indices analysis (3D-QSAR/CoMSIA) study on a series of 90 reported irreversible inhibitors of FAAH sharing a piperazine-carboxamide scaffold. The model obtained was extensively validated (q2 = 0.734; r2 = 0.966; r2m = 0.723). Finally, based on the information derived from the contour maps we designed a series of 10 new compounds with high predicted FAAH inhibition (predicted pIC50 of the best-proposed compounds = 12.196; 12.416). View Full-Text
Keywords: Fatty Acid Amide Hydrolase; cannabinoid; carboxamide inhibitors; 3D-QSAR; CoMSIA. Fatty Acid Amide Hydrolase; cannabinoid; carboxamide inhibitors; 3D-QSAR; CoMSIA.
Show Figures

Graphical abstract

MDPI and ACS Style

Lorca, M.; Valdes, Y.; Chung, H.; Romero-Parra, J.; Pessoa-Mahana, C.D.; Mella, J. Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) on a Series of Piperazine-Carboxamides Fatty Acid Amide Hydrolase (FAAH) Inhibitors as a Useful Tool for the Design of New Cannabinoid Ligands. Int. J. Mol. Sci. 2019, 20, 2510.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop