Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole Ring
Arylpiperazines represent one of the most important classes of 5-HT<sub>1A</sub>R ligands and have attracted considerable interests for their versatile properties in chemistry and pharmacology, leading to the research of new derivatives that has been focused on the modification of one or...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1483 |
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| author | Giorgia Andreozzi Maria Rosaria Ambrosio Elisa Magli Giovanni Maneli Beatrice Severino Angela Corvino Rosa Sparaco Elisa Perissutti Francesco Frecentese Vincenzo Santagada Anna Leśniak Magdalena Bujalska-Zadrożny Giuseppe Caliendo Pietro Formisano Ferdinando Fiorino |
| author_facet | Giorgia Andreozzi Maria Rosaria Ambrosio Elisa Magli Giovanni Maneli Beatrice Severino Angela Corvino Rosa Sparaco Elisa Perissutti Francesco Frecentese Vincenzo Santagada Anna Leśniak Magdalena Bujalska-Zadrożny Giuseppe Caliendo Pietro Formisano Ferdinando Fiorino |
| author_sort | Giorgia Andreozzi |
| collection | DOAJ |
| description | Arylpiperazines represent one of the most important classes of 5-HT<sub>1A</sub>R ligands and have attracted considerable interests for their versatile properties in chemistry and pharmacology, leading to the research of new derivatives that has been focused on the modification of one or more portions of such pharmacophore. An efficient protocol for the synthesis of novel thiazolinylphenyl-piperazines (<b>2a</b>–<b>c</b>) and the corresponding acetylated derivatives was used (<b>3a</b>–<b>c</b>). The new compounds were tested for their functional activity and affinity at 5-HT<sub>1A</sub> receptors, showing an interesting affinity profile with a Ki value of 412 nM for compound <b>2b</b>. The cytotoxic activity of novel thiazolinylphenyl-piperazines (<b>2a</b>–<b>c</b>) and corresponding N-acetyl derivatives (<b>3a</b>–<b>c</b>) against human prostate and breast cancer cell lines (LNCAP, DU-145 and PC-3, MCF-7, SKBR-3 and MDA-MB231) was investigated according to the procedure described in the literature. The reported data showed a cytotoxic effect for <b>2a</b>–<b>c</b> and <b>3a</b>–<b>c</b> compounds (IC<sub>50</sub> values ranging from 15 µM to 73 µM) on the investigated cancer cell lines, with no effect on noncancer cells. Future studies will be aimed to investigate the mechanism of action and therapeutic prospects of these new scaffolds. |
| first_indexed | 2024-03-10T20:59:12Z |
| format | Article |
| id | doaj.art-f809eadae0904facb28d7ccc4163c291 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:59:12Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-f809eadae0904facb28d7ccc4163c2912023-11-19T17:43:10ZengMDPI AGPharmaceuticals1424-82472023-10-011610148310.3390/ph16101483Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole RingGiorgia Andreozzi0Maria Rosaria Ambrosio1Elisa Magli2Giovanni Maneli3Beatrice Severino4Angela Corvino5Rosa Sparaco6Elisa Perissutti7Francesco Frecentese8Vincenzo Santagada9Anna Leśniak10Magdalena Bujalska-Zadrożny11Giuseppe Caliendo12Pietro Formisano13Ferdinando Fiorino14Dipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyURT “Genomic of Diabetes”, Institute for Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (IEOS-CNR), Via Pansini 5, 80131 Naples, ItalyDipartimento di Sanità Pubblica, Università di Napoli Federico II, Via Pansini, 5, 80131, Naples, ItalyDepartment of Translational Medicine, University of Naples “Federico II”, Via Pansini 5, 80131 Naples, ItalyDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyDepartment of Pharmacotherapy and Pharmaceutical Care, Centre for Preclinical Research and Technology, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, PolandDepartment of Pharmacotherapy and Pharmaceutical Care, Centre for Preclinical Research and Technology, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, PolandDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyURT “Genomic of Diabetes”, Institute for Experimental Endocrinology and Oncology “G. Salvatore”, National Research Council (IEOS-CNR), Via Pansini 5, 80131 Naples, ItalyDipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano, 49, 80131 Naples, ItalyArylpiperazines represent one of the most important classes of 5-HT<sub>1A</sub>R ligands and have attracted considerable interests for their versatile properties in chemistry and pharmacology, leading to the research of new derivatives that has been focused on the modification of one or more portions of such pharmacophore. An efficient protocol for the synthesis of novel thiazolinylphenyl-piperazines (<b>2a</b>–<b>c</b>) and the corresponding acetylated derivatives was used (<b>3a</b>–<b>c</b>). The new compounds were tested for their functional activity and affinity at 5-HT<sub>1A</sub> receptors, showing an interesting affinity profile with a Ki value of 412 nM for compound <b>2b</b>. The cytotoxic activity of novel thiazolinylphenyl-piperazines (<b>2a</b>–<b>c</b>) and corresponding N-acetyl derivatives (<b>3a</b>–<b>c</b>) against human prostate and breast cancer cell lines (LNCAP, DU-145 and PC-3, MCF-7, SKBR-3 and MDA-MB231) was investigated according to the procedure described in the literature. The reported data showed a cytotoxic effect for <b>2a</b>–<b>c</b> and <b>3a</b>–<b>c</b> compounds (IC<sub>50</sub> values ranging from 15 µM to 73 µM) on the investigated cancer cell lines, with no effect on noncancer cells. Future studies will be aimed to investigate the mechanism of action and therapeutic prospects of these new scaffolds.https://www.mdpi.com/1424-8247/16/10/1483arylpiperazines5-HT<sub>1A</sub> ligandsbinding assays, in vitro assay, cytotoxic activity |
| spellingShingle | Giorgia Andreozzi Maria Rosaria Ambrosio Elisa Magli Giovanni Maneli Beatrice Severino Angela Corvino Rosa Sparaco Elisa Perissutti Francesco Frecentese Vincenzo Santagada Anna Leśniak Magdalena Bujalska-Zadrożny Giuseppe Caliendo Pietro Formisano Ferdinando Fiorino Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole Ring Pharmaceuticals arylpiperazines 5-HT<sub>1A</sub> ligands binding assays, in vitro assay, cytotoxic activity |
| title | Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole Ring |
| title_full | Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole Ring |
| title_fullStr | Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole Ring |
| title_full_unstemmed | Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole Ring |
| title_short | Design, Synthesis and Biological Evaluation of Novel N-Arylpiperazines Containing a 4,5-Dihydrothiazole Ring |
| title_sort | design synthesis and biological evaluation of novel n arylpiperazines containing a 4 5 dihydrothiazole ring |
| topic | arylpiperazines 5-HT<sub>1A</sub> ligands binding assays, in vitro assay, cytotoxic activity |
| url | https://www.mdpi.com/1424-8247/16/10/1483 |
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