Synthesis, Docking Studies, Pharmacological Activity and Toxicity of a Novel Pyrazole Derivative (LQFM 021)—Possible Effects on Phosphodiesterase

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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 m<span style="font-variant: small-caps;">m</span>), the treatment with tetraethylammonium (TEA) (5 m<span style="font-variant: small-caps;">m</span>) 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.
公益社団法人日本薬学会の論文