title: Novel 1, 4-dihydropyridines for L-type calcium channel as antagonists for cadmium toxicity.
abstract: The 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, 5e showed 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, both in silico and in vitro results exploring two derivatives 5a and 5e succeeded to treat cadmium toxicity.
authors.affiliation: Division of Bioinformatics, Department of Zoology, Sri Venkateswara University, Tirupati, 517502, A.P., India.
authors.forename: Madhu Sudhana
authors.initials: MS
authors.lastname: Saddala
authors.affiliation: Garrison Institute on Aging, Texas Tech University of Health Science Centre, Lubbock, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kandimalla
authors.affiliation: Division of Bioinformatics, Department of Zoology, Sri Venkateswara University, Tirupati, 517502, A.P., India.|Garrison Institute on Aging, Texas Tech University of Health Science Centre, Lubbock, USA.
authors.forename: Pradeepkiran Jangampalli
authors.initials: PJ
authors.lastname: Adi
authors.affiliation: CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua dos Bragas, 177, 4050-123 Porto, Portugal.|Vikrama Simhapuri University, Nellore-524 003, Andhra Pradesh, India.
authors.forename: Sainath Sri
authors.initials: SS
authors.lastname: Bhashyam
authors.affiliation: Division of Bioinformatics, Department of Zoology, Sri Venkateswara University, Tirupati, 517502, A.P., India.
authors.forename: Usha Rani
authors.initials: UR
authors.lastname: Asupatri
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry*; D020134:Catalytic Domain; D002460:Cell Line; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D051381:Rats; D040681:Structural Homology, Protein
chemical_list: D000927:Anticonvulsants; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D002104:Cadmium; D002118:Calcium