RESUMO
This work evaluated the insecticidal, antifeedant and AChE inhibitory activity of compounds with eudesmane skeleton. The insecticidal activity was tested against larvae of Drosophila melanogaster and Cydia pomonella, the compounds 3 and 4 were the most active (LC50 of 104.2 and 106.7 µM; 82.0 and 84.4 µM, respectively). Likewise, the mentioned compounds were those that showed the highest acetylcholinesterase inhibitory activity, with IC50 of 0.26 ± 0.016 and 0.77 ± 0.016 µM, respectively. Enzyme kinetic studies, as well as molecular docking, show that the compounds would be non-competitive inhibitors of the enzyme. The antifeedant activity on Plodia interpunctella larvae showed an antifeedant index (AI) of 99% at 72 h for compounds 16, 27 and 20. The QSAR studies show that the properties associated with the polarity of the compounds would be responsible for the biological activities found.
Assuntos
Acetilcolinesterase , Inibidores da Colinesterase , Drosophila melanogaster , Inseticidas , Larva , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Sesquiterpenos de Eudesmano , Animais , Inseticidas/farmacologia , Inseticidas/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Larva/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos de Eudesmano/química , Mariposas/efeitos dos fármacos , Sesquiterpenos/farmacologia , Sesquiterpenos/químicaRESUMO
Natural cholinesterase inhibitors have been found in many biological sources. Nine compounds with agarofuran (epoxyeudesmane) skeletons were isolated from seeds and aerial parts of Maytenus disticha and Euonymus japonicus. The identification and structural elucidation of compounds were based on spectroscopic data analyses. All compounds had inhibitory acetylcholinesterase (AChE) activity. These natural compounds, which possessed mixed or uncompetitive mechanisms of inhibitory activity against AChE, may be considered as models for the design and development of new naturally occurring drugs for management strategies for neurodegenerative diseases. This is the first report of these chemical structures for seeds of M. disticha.