1. Synthesis, Docking Studies, Pharmacological Activity and Toxicity of a Novel Pyrazole Derivative (LQFM 021)—Possible Effects on Phosphodiesterase
- Author
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Soraya Santana de Moura, Matheus Lavorenti Rocha, Vinicius M. Alves, Carolina Horta Andrade, Marize Campos Valadares, Daniella Ramos Martins, Luciano M. Lião, Mariana Torquato Quezado de Magalhães, Francine Pazini, and Ricardo Menegatti
- Subjects
Male ,Models, Molecular ,Cell Survival ,Stereochemistry ,Tetrazoles ,Pharmacology ,Pyrazole ,Sarcoplasmic Reticulum Calcium-Transporting ATPases ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cyclic nucleotide ,Drug Discovery ,Animals ,Enzyme Inhibitors ,Rats, Wistar ,Tetraethylammonium ,Dose-Response Relationship, Drug ,Molecular Structure ,Phosphodiesterase ,Biological activity ,3T3 Cells ,General Chemistry ,General Medicine ,Cyclic Nucleotide Phosphodiesterases, Type 3 ,Acute toxicity ,Rats ,chemistry ,Docking (molecular) ,Toxicity ,Pyrazoles ,Nucleotides, Cyclic - Abstract
This study describes the synthetic route and molecular computational docking of LQFM 021, as well as examines its biological effects and toxicity. The docking studies revealed strong interaction of LQFM 021 to phosphodiesterase-3 (PDE-3). In isolated arteries, the presence of endothelium potentiates the relaxation for LQFM 021 and the inhibition cyclic nucleotides reduced the relaxation. Pre-contraction with KCl (45 mM), the treatment with tetraethylammonium (TEA) (5 mM) and inhibition of reticular Ca(2+)-ATPase showed an inhibitory effect on relaxation. Moreover, the compound reduced the contraction evoked by the Ca(2+) influx. Acute toxicity tests revealed that the compound was practically nontoxic. In conclusion, this study showed that a new synthetic derivative of pyrazole is a possible PDE-3 inhibitor and has vasorelaxant activity and low toxicity.
- Published
- 2013
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