Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities |
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| Authors: | Prof Alessia Carocci Dr Mariagrazia Roselli Prof Roberta Budriesi Dr Matteo Micucci Prof Jean-François Desaphy Dr Concetta Altamura Dr Maria Maddalena Cavalluzzi Dr Maddalena Toma Dr Giovanna Ilaria Passeri Dr Gualtiero Milani Dr Angelo Lovece Prof Alessia Catalano Dr Claudio Bruno Dr Annalisa De Palma Prof Filomena Corbo Prof Carlo Franchini Prof Solomon Habtemariam Prof Giovanni Lentini |
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| Affiliation: | 1. Department of Pharmacy – Pharmaceutical Sciences, University of Bari Aldo Moro, via E. Orabona n. 4, 70126 Bari, Italy;2. Department of Pharmacy and Biotechnologies, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, Bologna, 40126 Italy;3. Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, piazza Giulio Cesare, 70126 Bari, Italy;4. Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, via E. Orabona 4, 70126 Bari, Italy;5. Pharmacognosy Research Laboratories & Herbal Analysis services UK, University of Greenwich, Chatham-Maritime, Kent, ME4 4TB UK |
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| Abstract: | Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine. |
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