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.
Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism , Enzyme Inhibitors/pharmacology , Nucleotides, Cyclic/antagonists & inhibitors , Pyrazoles/pharmacology , Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & inhibitors , Tetrazoles/pharmacology , 3T3 Cells , Animals , Cell Survival/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Male , Mice , Models, Molecular , Molecular Structure , Nucleotides, Cyclic/metabolism , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Rats , Rats, Wistar , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Structure-Activity Relationship , Tetrazoles/chemical synthesis , Tetrazoles/chemistryABSTRACT
Ethanolic extracts from leaves of Hyptis ovalifolia, H. suaveolens, H. saxatilis, Hyptidendrum canum, Eugenia uniflora, E. dysenterica, Caryocar brasiliensis and Lafoensia pacari were investigated for their antifungal activity against dermatophytes. The most effective plants were H. ovalifolia and E. uniflora, while Trichophyton rubrum was the most sensitive among the four dermatophytes species evaluated. This study has demonstrated antifungal properties of Brazilian Cerrado plant extracts in "in vitro" assays.
A atividade antifúngica de extratos etanólicos de folhas de Hyptis ovalifolia, H. suaveolens, H. saxatilis, Hyptidendrum canum, Eugenia uniflora, E. dysenterica, Caryocar brasiliensis e Lafoensia pacari sobre isolados de dermatófitos foi verificada. Os extratos mais ativos foram os de H. ovalifolia e E. uniflora, enquanto que Trichophyton rubrum foi o dermatófito mais sensível a ação das plantas. Estes dados demonstram as propriedades antifúngicas de plantas do Cerrado em ensaios in vitro.