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Novel 1, 4-dihydropyridines for L-type calcium channel as antagonists for cadmium toxicity

Authors: Saddala, Madhu; Kandimalla, Ramesh; Adi, Pradeepkiran; Bhashyam, Sainath; Asupatri, Usha;

Novel 1, 4-dihydropyridines for L-type calcium channel as antagonists for cadmium toxicity

Abstract

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.

Countries
Portugal, United States
Keywords

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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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
29
Top 10%
Top 10%
Top 10%
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gold