Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment
As a follow-up to our previous studies on differently substituted 1,4-dihydropyridines endowed with a peculiar cardiac selectivity, in this paper, a small series of hybrid compounds bearing the pharmacophore fragment of lidoflazine in position 2 or 3 on a 4-(xanthen-9-one)-dihydropyridine core was r...
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MDPI AG
2018-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/23/12/3088 |
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| author | Alessandra Bisi Matteo Micucci Silvia Gobbi Federica Belluti Roberta Budriesi Angela Rampa |
| author_facet | Alessandra Bisi Matteo Micucci Silvia Gobbi Federica Belluti Roberta Budriesi Angela Rampa |
| author_sort | Alessandra Bisi |
| collection | DOAJ |
| description | As a follow-up to our previous studies on differently substituted 1,4-dihydropyridines endowed with a peculiar cardiac selectivity, in this paper, a small series of hybrid compounds bearing the pharmacophore fragment of lidoflazine in position 2 or 3 on a 4-(xanthen-9-one)-dihydropyridine core was reported. Lidoflazine was selected due to our promising previously reported data, and the xanthen-9-one substituent was introduced in position 4 of the dihydropyridine scaffold based on the cardiac selectivity observed in several of our studies. The new hybrid compounds were tested to assess cardiac and vascular activities, and the data were evaluated in comparison with those previously obtained for 4-(xanthen-9-one)-dihydropyridines and lidoflazine⁻nifedipine hybrid compounds. The functional studies indicated an interesting peculiar selectivity for the cardiac parameter inotropy, in particular when the lidoflazine fragment was introduced in position 2 of the dihydropyridine scaffold (<b>4a</b>⁻<b>e</b>), and thus a possible preferential binding with the Ca<sub>v</sub> 1.2 isoform of <span style="font-variant: small-caps;">l</span>-type calcium channels, which are mainly involved in cardiac contractility. |
| first_indexed | 2024-12-22T19:35:20Z |
| format | Article |
| id | doaj.art-6173268849ed41c8ae6fb83135f57cc5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T19:35:20Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6173268849ed41c8ae6fb83135f57cc52022-12-21T18:14:59ZengMDPI AGMolecules1420-30492018-11-012312308810.3390/molecules23123088molecules23123088Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore FragmentAlessandra Bisi0Matteo Micucci1Silvia Gobbi2Federica Belluti3Roberta Budriesi4Angela Rampa5Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro, 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro, 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro, 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro, 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro, 6, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro, 6, 40126 Bologna, ItalyAs a follow-up to our previous studies on differently substituted 1,4-dihydropyridines endowed with a peculiar cardiac selectivity, in this paper, a small series of hybrid compounds bearing the pharmacophore fragment of lidoflazine in position 2 or 3 on a 4-(xanthen-9-one)-dihydropyridine core was reported. Lidoflazine was selected due to our promising previously reported data, and the xanthen-9-one substituent was introduced in position 4 of the dihydropyridine scaffold based on the cardiac selectivity observed in several of our studies. The new hybrid compounds were tested to assess cardiac and vascular activities, and the data were evaluated in comparison with those previously obtained for 4-(xanthen-9-one)-dihydropyridines and lidoflazine⁻nifedipine hybrid compounds. The functional studies indicated an interesting peculiar selectivity for the cardiac parameter inotropy, in particular when the lidoflazine fragment was introduced in position 2 of the dihydropyridine scaffold (<b>4a</b>⁻<b>e</b>), and thus a possible preferential binding with the Ca<sub>v</sub> 1.2 isoform of <span style="font-variant: small-caps;">l</span>-type calcium channels, which are mainly involved in cardiac contractility.https://www.mdpi.com/1420-3049/23/12/3088xanthone1,4-dihydropyridinelidoflazinecalcium channelshybrid compounds |
| spellingShingle | Alessandra Bisi Matteo Micucci Silvia Gobbi Federica Belluti Roberta Budriesi Angela Rampa Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment Molecules xanthone 1,4-dihydropyridine lidoflazine calcium channels hybrid compounds |
| title | Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment |
| title_full | Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment |
| title_fullStr | Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment |
| title_full_unstemmed | Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment |
| title_short | Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment |
| title_sort | cardiovascular profile of xanthone based 1 4 dihydropyridines bearing a lidoflazine pharmacophore fragment |
| topic | xanthone 1,4-dihydropyridine lidoflazine calcium channels hybrid compounds |
| url | https://www.mdpi.com/1420-3049/23/12/3088 |
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