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New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and in Vitro Pharmacological Evaluation

Author(s):

Elisa Magli, Beatrice Severino*, Angela Corvino, Elisa Perissutti, Francesco Frecentese, Irene Saccone, Flavia Giordano, Marian Castro, Josè Brea, Marian Isabel Loza, Vincenzo Santagada, Giuseppe Caliendo and Ferdinando Fiorino   Pages 1 - 14 ( 14 )

Abstract:


Background: Serotonin is an important biogenic amine and is implicated in wide-ranging physiological and physiopathological processes. Pharmacological manipulation of the serotoninergic system in believed to have a great therapeutic potential.

Objective: In order to identify selective ligands for 5-HT1A, 5-HT2A and 5-HT2C receptors two series of 4-substituted piperazine derivatives, bearing indolic or methyl indolic nuclei, were synthesized.

Method: All the compounds, synthesized by standard solution methods, were evaluated towards 5-HT1A, 5-HT2A and 5-HT2C receptors. The highest affine and selective compounds have been evaluated also on dopaminergic (D1 and D2) and adrenergic (α1A and α2A) receptors.

Results: Several of the newly synthesized molecules showed affinity in the nanomolar range towards 5-HT1A, 5-HT2A and 5-HT2C receptors and moderate to no affinity for other relevant receptors (D1, D2, α1A and α2A).

Conclusion: Compounds 7f and 10a showed a nanomolar affinity towards 5-HT1A with an in vitro pharmacologic profile compatible with antipsychotic drugs.

Keywords:

Serotonin; Indolic and Methyl Indolic Nuclei; Arylpiperazine Derivatives; 5-HT1A, 5-HT2A and 5-HT2C Receptor Ligands; Synthesis; Binding assay.

Affiliation:

Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli,, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, Dipartimento di Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, USEF Screening Platform-BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela - 15782 Santiago de Compostela, USEF Screening Platform-BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela - 15782 Santiago de Compostela, USEF Screening Platform-BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela - 15782 Santiago de Compostela,, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli, Dipartimento di Farmacia - Università degli Studi di Napoli “Federico II”, Via D. Montesano, 49 - 80131, Napoli



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