Abstract
We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / chemical synthesis
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Analgesics / chemistry
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Analgesics / pharmacology*
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Animals
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology*
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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Arachidonic Acid / toxicity
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Arachidonic Acids / pharmacology
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Biphenyl Compounds / metabolism
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Brain / drug effects
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Cannabinoid Receptor Modulators / pharmacology
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Carrageenan / toxicity
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Cell Proliferation / drug effects
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Edema / chemically induced
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Edema / prevention & control
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Endocannabinoids
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Female
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Formaldehyde / toxicity
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Free Radical Scavengers / chemical synthesis
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Free Radical Scavengers / chemistry
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Free Radical Scavengers / pharmacology*
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Hydrazines / chemical synthesis*
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Hydrazines / chemistry
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Hydrazines / metabolism
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Hydrazines / pharmacology*
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Hydrazones / chemical synthesis*
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Hydrazones / chemistry
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Hydrazones / pharmacology
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Ligands
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Male
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Mice
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Models, Molecular
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Pain / drug therapy
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Picrates
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Polyunsaturated Alkamides / pharmacology
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Pyridines / toxicity
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Rats
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Rats, Wistar
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / metabolism*
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Receptor, Cannabinoid, CB2 / agonists
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Receptor, Cannabinoid, CB2 / metabolism*
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Structure-Activity Relationship
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Superoxides / metabolism
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T-Lymphocytes / drug effects
Substances
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Analgesics
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Anti-Inflammatory Agents
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Antioxidants
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Arachidonic Acids
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Biphenyl Compounds
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Cannabinoid Receptor Modulators
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Endocannabinoids
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Free Radical Scavengers
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Hydrazines
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Hydrazones
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LASSBio-881
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Ligands
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Picrates
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Polyunsaturated Alkamides
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Pyridines
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Receptor, Cannabinoid, CB1
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Receptor, Cannabinoid, CB2
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tris(2-pyridylmethyl)amine
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Superoxides
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Formaldehyde
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Arachidonic Acid
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Carrageenan
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1,1-diphenyl-2-picrylhydrazyl
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anandamide