1,4-dihydropyridine; Sulfonylurea; Thiourea; Urea; Vasodilator activity; Voltage-gated calcium channel blockers; Biochemistry; Chemistry (all); Chemical Engineering (all); Industrial and Manufacturing Engineering; Materials Chemistry; General Chemical Engineering; General Chemistry
Abstract :
[en] Abstract: Some new 1,4-dihydropyridines bearing sulfonylurea, urea and thiourea moieties were synthesized and pharmacologically evaluated for their vasodilator activity, comparatively to nifedipine and diazoxide. The investigations of the target compounds on rat aorta rings showed that, except the sulfonylureas derivatives, which were inactive (EC50 > 100 μΜ), ureas and thioureas derivatives showed moderate to strong vasodilator activity, with EC50 values varying from 1.2 to 40 μM. 17-fold more active than diazoxide (but less active than nifedipine), the most active compound (1.2 ± 0.2 μM) was found to be a voltage-gated calcium channels blocker, as it is the case for the reference compound, nifedipine. The results also showed that an aliphatic or aromatic R group (the latter bearing electro-donating or electro-withdrawing substituents) gave very active compounds. The inactiveness of sulfonylurea derivatives could be explained by a partial ionization at physiological pH because of their weak acid character. Finally, it would be very suitable to synthesize N-methylated analogs of sulfonylurea derivatives, and more urea and thiourea derivatives bearing aliphatic R groups, and to test them on the same pharmacological model. Therefore, the series of 1,4-dihydropyridines described herein displayed good potential for the development of new vasodilator agents in the search for new therapeutics for the treatment of some cardiovascular diseases. Graphic abstract: [Figure not available: see fulltext.].
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Stiti, Mohamed Zakaria; Laboratory of Phytochemistry and Pharmacology, Department of Chemistry, Faculty of Exact Sciences and Informatics, University of Mohamed Seddik Ben Yahia Jijel, Jijel, Algeria ; Laboratory of Pharmaceutical Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liège, Belgium
Belghobsi, Mebrouk; Laboratory of Phytochemistry and Pharmacology, Department of Chemistry, Faculty of Exact Sciences and Informatics, University of Mohamed Seddik Ben Yahia Jijel, Jijel, Algeria
Habila, Tahir; Laboratory of Phytochemistry and Pharmacology, Department of Chemistry, Faculty of Exact Sciences and Informatics, University of Mohamed Seddik Ben Yahia Jijel, Jijel, Algeria ; Laboratory of Pharmaceutical Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liège, Belgium
Goffin, Eric ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
De Tullio, Pascal ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Pirotte, Bernard ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Faury, Gilles; Laboratory of ‘Hypoxy_ Cardiovascular and Respiratory Physiopathology’ (HP2), INSERM U1042-University of Grenoble-Alpes, La Tronche, France
Khelili, Smail ; Laboratory of Phytochemistry and Pharmacology, Department of Chemistry, Faculty of Exact Sciences and Informatics, University of Mohamed Seddik Ben Yahia Jijel, Jijel, Algeria
Language :
English
Title :
Synthesis and vasodilator activity of new 1,4-dihyropyridines bearing sulfonylurea, urea and thiourea moieties
This work was supported by the Algerian Ministry of Higher Education and Scientific Research, Laboratory of Phytochemistry and Pharmacology (University of Mohamed Seddik Ben Yahia, Jijel-Algeria), Laboratory of Pharmaceutical chemistry (University of Liège-Belgium), and HP2 Laboratory (University of Grenoble-Alpes, France). The authors gratefully acknowledge the technical assistance of Stéphane Counerotte, Sandrine Cachot, Bouraoui Hadia and Aibech Riad.
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