title: Synthesis, docking studies, pharmacological activity and toxicity of a novel pyrazole derivative (LQFM 021)--possible effects on phosphodiesterase.
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.
authors: Faculty of Pharmacy, Federal University of Goias, Av. Universitária s/n, 74605-220 Goiânia, GO, Brazil.
authors: Daniella
authors: D
authors: Ramos Martins
authors: Francine
authors: F
authors: Pazini
authors: Vinícius
authors: V
authors: de Medeiros Alves
authors: Soraya
authors: S
authors: Santana de Moura
authors: Luciano
authors: L
authors: Morais Lião
authors: Mariana
authors: M
authors: Torquato Quezado de Magalhães
authors: Marize
authors: M
authors: Campos Valadares
authors: Carolina
authors: C
authors: Horta Andrade
authors: Ricardo
authors: R
authors: Menegatti
authors: Matheus
authors: M
authors: Lavorenti Rocha
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009712:Nucleotides, Cyclic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C585652:5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole; D004791:Enzyme Inhibitors; D009712:Nucleotides, Cyclic; D011720:Pyrazoles; D013777:Tetrazoles; C031280:pyrazole; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases