
AbstractThe present study, we design and synthesize the novel dihydropyridine derivatives, i.e., 3 (a-e) and 5 (a-e) and evaluated, anticonvulsant activity. Initially due to the lacuna of LCC, we modeled the protein through modeller 9.15v and evaluated through servers. Docking studies were performed with the synthesized compounds and resulted two best compounds, i.e.,5a, 5eshowed the best binding energies. The activity of intracellular Ca2+measurements was performed on two cell lines: A7r5 (rat aortic smooth muscle cells) and SH-SY5Y (human neuroblastoma cells). The 5a and 5e compounds was showing the more specific activity on L-type calcium channels, i.e. A7r5 (IC50 = 0.18 ± 0.02 and 0.25 ± 0.63 μg/ml, respectively) (containing only L-type channels) than SH-SY5Y (i.e. both L-type and T-type channels) (IC50 = 8 ± 0.23 and 10 ± 0.18 μg/ml, respectively) with intracellular calcium mobility similar to amlodipine. Finally, bothin silicoandin vitroresults exploring two derivatives 5a and 5e succeeded to treat cadmium toxicity.
Models, Molecular, Dihydropyridines, Calcium Channels, L-Type, 610, Apoptosis, Article, Cell Line, Models, Catalytic Domain, Animals, Humans, Structural Homology, Protein, Molecular, L-Type, 620, Rats, Molecular Docking Simulation, Structural Homology, Protein, Anticonvulsants, Calcium, Calcium Channels, Cadmium
Models, Molecular, Dihydropyridines, Calcium Channels, L-Type, 610, Apoptosis, Article, Cell Line, Models, Catalytic Domain, Animals, Humans, Structural Homology, Protein, Molecular, L-Type, 620, Rats, Molecular Docking Simulation, Structural Homology, Protein, Anticonvulsants, Calcium, Calcium Channels, Cadmium
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