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Partial QSAR analysis of some selected natural inhibitors of FAAH suggests a working hypothesis for the development of endocannabinoid-based drugs.

Abstract

The endogenous cannabinoids (endocannabinoids) are bioactive signaling molecules, that show diverse cellular and physiological effects and play various roles in the central nervous system, as well as in the periphery. The discovery of N-arachidonoylethanolamine (anandamide, AEA) and of the enzyme that terminates its signaling, i. e. fatty acid amide hydrolase (FAAH), has inspired pharmacological strategies to augment endocannabinoid tone and biological activity through inhibition of FAAH. Here we discuss the role of natural endocannabinoid derivatives, like the hydroxy-anandamides (OH-AEAs) generated from AEA via lipoxygenase activity, as powerful inhibitors of FAAH. We propose that these compounds, by reversibly inhibiting FAAH, may control in vivo the endocannabinoid tone. We consider the theoretical structural properties of OH-AEAs and other natural inhibitors of FAAH, based on the calculation of theoretical molecular descriptors commonly used in Quantitative Structure Activity Relationship (QSAR) studies. The QSAR properties of OH-AEAs and congeners suggest that they could act at different specific sites of FAAH, thus confirming their potential value as templates for the development of next-generation therapeutics.

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  • Authors+Show Affiliations

    ,

    Department of Biomedical Sciences, University of Teramo, Piazza Aldo Moro 45, 64100 Teramo, Italy.

    ,

    Source

    MeSH

    Amidohydrolases
    Animals
    Cannabinoid Receptor Modulators
    Endocannabinoids
    Humans
    Structure-Activity Relationship
    Technology, Pharmaceutical

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    16375688

    Citation

    Dainese, Enrico, et al. "Partial QSAR Analysis of some Selected Natural Inhibitors of FAAH Suggests a Working Hypothesis for the Development of Endocannabinoid-based Drugs." Current Drug Targets. CNS and Neurological Disorders, vol. 4, no. 6, 2005, pp. 709-14.
    Dainese E, Gasperi V, Maccarrone M. Partial QSAR analysis of some selected natural inhibitors of FAAH suggests a working hypothesis for the development of endocannabinoid-based drugs. Curr Drug Targets CNS Neurol Disord. 2005;4(6):709-14.
    Dainese, E., Gasperi, V., & Maccarrone, M. (2005). Partial QSAR analysis of some selected natural inhibitors of FAAH suggests a working hypothesis for the development of endocannabinoid-based drugs. Current Drug Targets. CNS and Neurological Disorders, 4(6), pp. 709-14.
    Dainese E, Gasperi V, Maccarrone M. Partial QSAR Analysis of some Selected Natural Inhibitors of FAAH Suggests a Working Hypothesis for the Development of Endocannabinoid-based Drugs. Curr Drug Targets CNS Neurol Disord. 2005;4(6):709-14. PubMed PMID: 16375688.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Partial QSAR analysis of some selected natural inhibitors of FAAH suggests a working hypothesis for the development of endocannabinoid-based drugs. AU - Dainese,Enrico, AU - Gasperi,Valeria, AU - Maccarrone,Mauro, PY - 2005/12/27/pubmed PY - 2006/2/8/medline PY - 2005/12/27/entrez SP - 709 EP - 14 JF - Current drug targets. CNS and neurological disorders JO - Curr Drug Targets CNS Neurol Disord VL - 4 IS - 6 N2 - The endogenous cannabinoids (endocannabinoids) are bioactive signaling molecules, that show diverse cellular and physiological effects and play various roles in the central nervous system, as well as in the periphery. The discovery of N-arachidonoylethanolamine (anandamide, AEA) and of the enzyme that terminates its signaling, i. e. fatty acid amide hydrolase (FAAH), has inspired pharmacological strategies to augment endocannabinoid tone and biological activity through inhibition of FAAH. Here we discuss the role of natural endocannabinoid derivatives, like the hydroxy-anandamides (OH-AEAs) generated from AEA via lipoxygenase activity, as powerful inhibitors of FAAH. We propose that these compounds, by reversibly inhibiting FAAH, may control in vivo the endocannabinoid tone. We consider the theoretical structural properties of OH-AEAs and other natural inhibitors of FAAH, based on the calculation of theoretical molecular descriptors commonly used in Quantitative Structure Activity Relationship (QSAR) studies. The QSAR properties of OH-AEAs and congeners suggest that they could act at different specific sites of FAAH, thus confirming their potential value as templates for the development of next-generation therapeutics. SN - 1568-007X UR - https://www.unboundmedicine.com/medline/citation/16375688/Partial_QSAR_analysis_of_some_selected_natural_inhibitors_of_FAAH_suggests_a_working_hypothesis_for_the_development_of_endocannabinoid_based_drugs_ L2 - http://www.eurekaselect.com/90423/article DB - PRIME DP - Unbound Medicine ER -