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Your search keyword '"Arribas RL"' showing total 2 results
Start Over Author "Arribas RL" Topic calcium channel blockers
2 results on '"Arribas RL"'

1. New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H 3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition.

Author

Malek R, Arribas RL, Palomino-Antolin A, Totoson P, Demougeot C, Kobrlova T, Soukup O, Iriepa I, Moraleda I, Diez-Iriepa D, Godyń J, Panek D, Malawska B, Głuch-Lutwin M, Mordyl B, Siwek A, Chabchoub F, Marco-Contelles J, Kiec-Kononowicz K, Egea J, de Los Ríos C, and Ismaili L

Subjects
Alzheimer Disease metabolism, Animals, Calcium Channel Blockers chemistry, Cholinesterase Inhibitors chemistry, Humans, Memory Disorders drug therapy, Memory Disorders metabolism, Mice, Neuroblastoma drug therapy, Neuroblastoma metabolism, Neuroprotective Agents chemistry, Small Molecule Libraries chemistry, Tumor Cells, Cultured, Vasodilator Agents chemistry, Alzheimer Disease drug therapy, Calcium Channel Blockers pharmacology, Cholinesterase Inhibitors pharmacology, Neuroprotective Agents pharmacology, Receptors, Histamine H3 chemistry, Small Molecule Libraries pharmacology, Vasodilator Agents pharmacology
Abstract

New tritarget small molecules combining Ca 2+ channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound 3p has been identified as a very promising lead, showing good Ca 2+ channels blockade activity (IC 50 = 21 ± 1 μM), potent affinity against hH3R ( K i = 565 ± 62 nM), a moderate but selective hBuChE inhibition (IC 50 = 7.83 ± 0.10 μM), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lipopolysaccharide.

Published
2019
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2. Substituent effect of N-benzylated gramine derivatives that prevent the PP2A inhibition and dissipate the neuronal Ca 2+ overload, as a multitarget strategy for the treatment of Alzheimer's disease.

Author

Gonzalez D, Arribas RL, Viejo L, Lajarin-Cuesta R, and de Los Rios C

Subjects
Alkaloids chemical synthesis, Alkaloids chemistry, Alkaloids pharmacology, Alkaloids toxicity, Calcium metabolism, Calcium Channel Blockers chemical synthesis, Calcium Channel Blockers chemistry, Calcium Channel Blockers toxicity, Cell Line, Tumor, Humans, Indole Alkaloids chemical synthesis, Indole Alkaloids chemistry, Indoles chemical synthesis, Indoles chemistry, Indoles toxicity, Molecular Docking Simulation, Molecular Structure, Neurons metabolism, Neuroprotective Agents chemical synthesis, Neuroprotective Agents chemistry, Neuroprotective Agents toxicity, Okadaic Acid pharmacology, Piperidines chemical synthesis, Piperidines chemistry, Piperidines toxicity, Protein Phosphatase 2 antagonists & inhibitors, Structure-Activity Relationship, Alzheimer Disease drug therapy, Calcium Channel Blockers pharmacology, Indole Alkaloids pharmacology, Indoles pharmacology, Neuroprotective Agents pharmacology, Piperidines pharmacology, Protein Phosphatase 2 metabolism
Abstract

Following the premises of the multitarget-directed ligands approach for the drug R&D against neurodegenerative diseases, where Alzheimer's disease (AD) outstands, we have synthesized and evaluated analogues of the gramine derivative ITH12657 (1-benzyl-5-methyl-3-(piperidin-1-ylmethyl-1H-indole, 2), which had shown important neuroprotective properties, such as blocking effect of voltage-gated Ca 2+ channels (VGCC), and prevention of phosphoprotein phosphatase 2A (PP2A) inhibition. The new analogues present different substitutions at the pending phenyl ring, what slightly modified their pharmacological characteristics. The VGCC blockade was enhanced in derivatives possessing nitro groups, while the pro-PP2A feature was ameliorated by the presence of fluorine. Chlorine atoms supplied good activities over the two biological targets aimed; nevertheless that substitution provoked loss of viability at 100-fold higher concentrations (10 μM), what discards them for a deeper pharmacological study. Overall, the para-fluorine derivative of ITH12657 was the most promising candidate for further preclinical assays., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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