Synthesis, Docking Studies and Pharmacological Evaluation of Serotoninergic Ligands Containing a 5-Norbornene-2-Carboxamide Nucleus

被引：6

作者：

Sparaco, Rosa ^{[1
]}

Kedzierska, Ewa ^{[2
]}

Kaczor, Agnieszka A. ^{[3
,4
]}

Bielenica, Anna ^{[5
]}

Magli, Elisa ^{[6
]}

Severino, Beatrice ^{[1
]}

Corvino, Angela ^{[1
]}

Gibula-Tarlowska, Ewa ^{[2
]}

Kotlinska, Jolanta H. ^{[2
]}

Andreozzi, Giorgia ^{[1
]}

Luciano, Paolo ^{[1
]}

Perissutti, Elisa ^{[1
]}

Frecentese, Francesco ^{[1
]}

Casertano, Marcello ^{[1
]}

Lesniak, Anna ^{[7
]}

Bujalska-Zadrozny, Magdalena ^{[7
]}

Ozieblo, Malgorzata ^{[7
]}

Capasso, Raffaele ^{[8
]}

Santagada, Vincenzo ^{[1
]}

Caliendo, Giuseppe ^{[1
]}

Fiorino, Ferdinando ^{[1
]}

机构：

[1] Univ Napoli Federico II, Dipartimento Farm, Via Montesano, I-80131 Naples, Italy

[2] Med Univ Lublin, Fac Pharm Div Med Analyt, Dept Pharmacol & Pharmacodynam, 4A Chodzki St, PL-20093 Lublin, Poland

[3] Med Univ Lublin, Fac Pharm, Dept Synth & Chem Technol Pharmaceut Subst Comp M, 4A Chodzki St, PL-20093 Lublin, Poland

[4] Univ Eastern Finland, Sch Pharm, POB 1627, Kuopio 70211, Finland

[5] Med Univ Warsaw, Chair & Dept Biochem, PL-02097 Warsaw, Poland

[6] Univ Napoli Federico Ii, Dipartimento Sanita Pubbl, Via Pansini 5, I-80131 Naples, Italy

[7] Med Univ Warsaw, Fac Pharm, Ctr Preclin Res & Technol, Dept Pharmacodynam, 1b Banacha Str, PL-02097 Warsaw, Poland

[8] Univ Napoli Federico II, Dipartimento Agr, Via Univ, I-80055 Portici, Italy

来源：

MOLECULES | 2022年 / 27卷 / 19期

关键词：

5-norbornene-2-carboxilic acid; serotonin; arylpiperazine derivatives; 5-HT1A; 5-HT2A and 5-HT2C receptor ligands; ACTIVATED PROTEIN-KINASE; 5-HT1A RECEPTOR LIGANDS; IN-VITRO; 5-HYDROXYTRYPTAMINE(1A) RECEPTOR; STRUCTURAL BASIS; PLUS-MAZE; ANTIDEPRESSANT; DERIVATIVES; ANXIETY; MODELS;

D O I：

10.3390/molecules27196492

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new series of 5-norbornene-2-carboxamide derivatives was prepared and their affinities to the 5-HT1A, 5-HT2A, and 5-HT2C receptors were evaluated and compared to a previously synthesized series of derivatives characterized by exo-N-hydroxy-5-norbornene-2,3-dicarboximidenucleus, in order to identify selective ligands for the above-mentioned subtype receptors. Arylpiperazines represents one of the most important classes of 5-HT1AR ligands, and recent research concerning new derivatives has been focused on the modification of one or more portions of such pharmacophore. The combination of structural elements (heterocyclic nucleus, propyl chain and 4-substituted piperazine), known to be critical to the affinity to 5-HT1A receptors, and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. The most active compounds were selected for further in vivo assays to determine their functional activity. Finally, to rationalize the obtained results, molecular docking studies were performed. The results of the pharmacological studies showed that Norbo-4 and Norbo-18 were the most active and promising derivatives for the serotonin receptor considered in this study.

引用

页数：39

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