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Novel 11,12H-dihydronaphthalene[1,2-b]quinoline as Atypical Antipsychotic

[ Vol. 15 , Issue. 3 ]

Author(s):

Maria Matilde Ramirez Moran, Jorge Eduardo Angel Guio*, Natividad Herrera Cano, Biagina del Carmen Migliore, Rodolfo Izquierdo, Jaime Charris, Simon Lopez, Anita Israel, Ana Santiago, Roberto Rossi, Luis Perdomo, Akram Samear Dabian, Mariagracia Vera Sosa, Alejandra Villalba and Ligia Biagina Angel Migliore   Pages 294 - 303 ( 10 )

Abstract:


Background: Neurodegenerative, neurological and mental disorders, as well as substance abuse have a worldwide high incidence rate, becoming relevant factors that contribute to premature morbidity and mortality. Dopamine is well known to be involved in these pathologies. The key focus in the search for new drugs, that alleviate or cure these diseases, is pursuing the design of compounds with both efficacy and fewer adverse effects in order to obtain novel agents capable of restoring the homeostasis in the CNS of dopaminergic neurotransmission and counteracting some of neurodegenerative and neuropsychiatric diseases, such as Parkinson's disease, schizophrenia, Huntington's chorea and drug addictions.

Methods: the compounds 11,12H-dihydronaphthalene[1,2-b] quinoline 2a and 9-methoxy-11,12Hdihydronaphthalene [1,2-b] quinoline 2b were designed and synthesized. The organic synthesis was performed according to the outlined synthesis strategies, together with a pharmacological evaluation of the male Sprague-Dawley rats.

Results: Compound structures were confirmed by 1H, 13C, DEPT and HETCOR NMR. Pharmacological testing and computational studies validated the asserted medicinal-chemical approach for their design, showing compound 2a acting as an atypical dopamine antagonist.

Conclusion: The study showed that compound 2a has an atypical antagonistic action on the central dopaminergic system. These pharmacological and computational-theoretical results support the suitability of the medicinal chemical approach in the design of this compound.

Keywords:

Dopamine, schizophrenia, atypical antipsychotic, stereotypy, quinoline, molecular dynamics simulations.

Affiliation:

Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, INFIQC, Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Laboratorio de Quimica Teorica y Computacional, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Laboratorio de Sintesis Organica, Departament of Chemistry, University of Florida, P.O. Box 117200, Gainesville, Florida, 32611-7200, Laboratorio de Neuropeptidos, Facultad de Farmacia, Universidad Central de Venezuela, Caracas, INFIQC, Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, INFIQC, Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Laboratorio de Sintesis Organica, Diseno y Evaluacion Farmacologica de Nuevos Productos, Departamento de Quimica, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo

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