Article
Synthesis, docking studies, pharmacological activity and toxicity of a novel pyrazole derivative (LQFM 021): possible effects on phosphodiesterase
Registro en:
MOURA, Soraya Santana de et al. Synthesis, docking studies, pharmacological activity and toxicity of a novel pyrazole derivative (LQFM 021)--possible effects on phosphodiesterase. Chemical and Pharmaceutical Bulletin, v. 61, n. 5, p. 524-531, 2013.
0009-2363
10.1248/cpb.c12-01016
1347-5223
Autor
Martins, Daniella Ramos
Pazini, Francine
Alves, Vinícius de Medeiros
Moura, Soraya Santana de
Lião, Luciano Morais
Magalhães, Mariana Torquato Quezado de
Valadares, Marize Campos
Andrade, Carolina Horta
Menegatti, Ricardo
Rocha, Matheus Lavorenti
Resumen
Soraya Santana de Moura. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento. 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 (45mm),
the treatment with tetraethylammonium (TEA) (5mm) and inhibition of reticular Ca2+-ATPase showed an
inhibitory effect on relaxation. Moreover, the compound reduced the contraction evoked by the Ca2+ 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.