RESUMO
The repellent capacity against Sitophilus zeamais and the in vitro inhibition on AChE of 11 essential oils, isolated from six plants of the northern region of Colombia, were assessed using a modified tunnel-type device and the Ellman colorimetric method, respectively. The results were as follows: (i) the degree of repellency (DR) of the EOs against S. zeamais was 20-68% (2 h) and 28-74% (4 h); (ii) the IC50 values on AChE were 5-36 µg/mL; likewise, the %inh. on AChE (1 µg/cm3 per EO) did not show any effect in 91% of the EO tested; (iii) six EOs (Bursera graveolens-bark, B. graveolens-leaves, B. simaruba-bark, Peperomia pellucida-leaves, Piper holtonii (1b*)-leaves, and P. reticulatum-leaves) exhibited a DR (53-74%) ≥ C+ (chlorpyrifos-61%), while all EOs were less active (8-60-fold) on AChE compared to chlorpyrifos (IC50 of 0.59 µg/mL). Based on the ANOVA/linear regression and multivariate analysis of data, some differences/similarities could be established, as well as identifying the most active EOs (five: B. simaruba-bark, Pep. Pellucida-leaves, P. holtonii (1b*)-leaves, B. graveolens-bark, and B. graveolens-leaves). Finally, these EOs were constituted by spathulenol (24%)/ß-selinene (18%)/caryophyllene oxide (10%)-B. simaruba; carotol (44%)/dillapiole (21%)-Pep. pellucida; dillapiole (81% confirmed by 1H-/13C-NMR)-P. holtonii; mint furanone derivative (14%)/mint furanone (14%)-B. graveolens-bark; limonene (17%)/carvone (10%)-B. graveolens-leaves.
Assuntos
Inibidores da Colinesterase , Repelentes de Insetos , Óleos Voláteis , Sesquiterpenos Policíclicos , Animais , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Colômbia , Repelentes de Insetos/farmacologia , Repelentes de Insetos/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Piper/química , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/farmacologia , Gorgulhos/enzimologia , Gorgulhos/efeitos dos fármacos , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Tetraethyl pyrophosphate (TEPP) is an organophosphate pesticide that irreversibly inhibits acetylcholinesterase (AChE). Cork powder or granules have been recommended as a sustainable sorbent to remove pesticides from water. In the present study, we evaluated the effectiveness of removing TEPP from water using wine corks to obtain cork granules as natural adsorbent, analyzing the TEPP effects on AChE activity in commercial enzyme from Electrophorus electricus and secreted by neuronal PC12 cells. TEPP inhibited AChE activity in a concentration-dependent manner. For the first time, we showed that different concentrations of TEPP diluted in water after adsorption experiments using cork granules decreased TEPP's inhibitory effects on AChE activity in commercial enzyme and neuronal PC12 cell culture medium. Our results suggest that the optimum removal of TEPP from water by corks was 91.4 ± 4.0%. Overall, the findings support the hypothesis that cork granules can be used to remediate pesticide-contaminated environments, such as those contaminated by organophosphate pesticides, and demonstrate a new application of a biochemical assay on AChE activity using a commercial enzyme or secreted by neuronal PC12 cells in culture as a possible methodologic strategy for evaluating the success of TEPP removal from water.
Assuntos
Acetilcolinesterase , Praguicidas , Animais , Organofosfatos , Compostos Organofosforados , Células PC12 , Praguicidas/farmacologia , Ratos , ÁguaRESUMO
The aim of this work was to test the insecticidal effect of the essential oil of Illicium verum (Hook) by observing the survival, biochemical parameters (acetylcholinesterase (AChE) activity, glutathione s-transferase (GST) activity and the concentration of reactive oxygen species (ROS)) and locomotor capacity of the Coleoptera Alphitobius diaperinus (Panzer), a pest of beef poultry. The sublethal concentrations (100% survival of A. diaperinus during 96 h of exposure) of I. verum essential oil selected for analysis were 0.5% and 1%. The selected sublethal concentrations did not show significant increases in ROS levels after 24 h of exposure to the essential oil. However, increases in GST activity were seen following exposure to 0.5% I. verum essential oil, while decreases in AChE activity were observed following exposure to concentrations of 0.5% and 1%. These results correlate with the observed behavior of A. diaperinus; when placed into an arena, these insects typically demonstrate aversion to stimuli and refuge-seeking behavior. Following exposure to 0.5% I. verum essential oil, the insects showed loss of refuge-seeking capacity and, following exposure to a concentration of 1%, loss of locomotor capacity. Overall, these results indicate that I. verum essential oil can be used as an alternative to conventional insecticides.
Assuntos
Besouros , Illicium , Inseticidas , Óleos Voláteis , Acetilcolinesterase , Animais , Bovinos , Colinesterases , Inseticidas/farmacologia , Locomoção , Óleos Voláteis/farmacologiaRESUMO
Abstract The purpose of this study was to investigate the relationship between the acetylcholinesterase (AChE) inhibitory and antigenotoxic effect with the neuroprotective activity of Glaucium corniculatum methanol and water extracts rich in rutin and quercetin flavonoids. Neuroprotective activity in terms of cell survival and development against oxidative damage was measured by MTT assay and microscopic analysis in H2O2-induced NGF-differentiated PC12 (dPC12) cells. QRT-PCR and western blot hybridization method was employed for the determination of AChE inhibition of the extracts in the same cell model, and the genotoxic and antigenotoxic effects were identified with Comet assay with human lymphocytes. H2O2-induced vitality loss in dPC12 cells was inhibited in pre-treated cells with these plant extracts. Moreover, extracts stimulated neurite formation and prevented the oxidative stress-induced reduction in neurite growth. In general, it was determined that G. corniculatum methanol extract containing higher amounts of rutin and quercetin was more effective than water extract in terms of AChE inhibitory, antigenotoxic and also neuroprotective effect. In this study, it was shown for the first time that both AChE inhibitory and antigenotoxic effects of G. corniculatum may be effective in neuroprotection and it's protective and therapeutic effects against neurodegeneration may be related to the flavonoid content.
Assuntos
Acetilcolinesterase/efeitos adversos , Extratos Vegetais/agonistas , Papaveraceae/classificação , Neuroproteção , Dor/classificação , Flavonoides/farmacologia , Western Blotting , Fármacos NeuroprotetoresRESUMO
Rhinella schneideri is a common toad found in South America, whose paratoid toxic secretion has never been explored as an insecticide. In order to evaluate its insecticidal potential, Nauphoeta cinerea cockroaches were used as an experimental model in biochemical, physiological and behavioral procedures. Lethality assays with Rhinella schneideri paratoid secretion (RSPS) determined the LD50 value after 24 h (58.07µg/g) and 48 h exposure (44.07 µg/g) (R2 = 0.882 and 0.954, respectively). Acetylcholinesterase activity (AChE) after RSPS at its highest dose promoted an enzyme inhibition of 40%, a similar effect observed with neostigmine administration (p < 0.001, n= 5). Insect locomotion recordings revealed that RSPS decreased the distance traveled by up to 37% with a concomitant 85% increase in immobile episodes (p < 0.001, n = 36). RSPS added to in vivo cockroach semi-isolated heart preparation promoted an irreversible and dose dependent decrease in heart rate, showing a complete failure after 30 min recording (p < 0.001, n ≥ 6). In addition, RSPS into nerve-muscle preparations induced a dose-dependent neuromuscular blockade, reaching a total blockage at 70 min at the highest dose applied (p < 0.001, n ≥ 6). The effect of RSPS on spontaneous sensorial action potentials was characterized by an increase in the number of spikes 61% (p < 0.01). Meanwhile, there was 42% decrease in the mean area of those potentials (p < 0.05, n ≥ 6). The results obtained here highlight the potential insecticidal relevance of RSPS and its potential biotechnological application.
Assuntos
Venenos de Anfíbios/farmacologia , Bufo marinus/metabolismo , Inibidores da Colinesterase/farmacologia , Baratas/efeitos dos fármacos , Inseticidas/farmacologia , Junção Neuromuscular/efeitos dos fármacos , Glândula Parótida/metabolismo , Acetilcolinesterase/metabolismo , Venenos de Anfíbios/metabolismo , Animais , Inibidores da Colinesterase/metabolismo , Baratas/enzimologia , Relação Dose-Resposta a Droga , Feminino , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/metabolismo , Inseticidas/metabolismo , Dose Letal Mediana , Locomoção/efeitos dos fármacos , Masculino , Junção Neuromuscular/enzimologia , Via SecretóriaRESUMO
We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.
Assuntos
Simulação por Computador/classificação , Salmonella typhi/classificação , Sulfonamidas/efeitos adversos , Tioureia , Bacillus subtilis/classificação , Urease , Soroalbumina Bovina , Preparações Farmacêuticas/administração & dosagem , Inibidores da Colinesterase/farmacologia , Concentração Inibidora 50 , Espectroscopia de Prótons por Ressonância Magnética/métodos , Análise de Dados , Aminoácidos/antagonistas & inibidoresRESUMO
Jacaranda oxyphylla Cham. (Bignoniaceae) is a shrub found in the Brazilian cerrado and used in folk medicine to treat microbial infections. The aim of this study was to carry out a phytochemical screening and evaluate antioedematogenic, antimicrobial and antiacetylcholinesterase properties of J. oxyphylla crude extracts. All extracts analysed showed presence of terpenoids, which are potentially active chemical substances. A high AChE inhibitory activity for hexane extract from leaves and for the extracts from twigs was found. Ethanol extract from leaves of J. oxyphylla showed activity against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli) bacteria. This extract was also effective in inhibiting the stages of inflammation evaluated. Biological investigation and phytochemical screening of J. oxyphylla extracts provided additional evidence of its traditional medicinal value.
Assuntos
Antibacterianos/farmacologia , Bignoniaceae/química , Inibidores da Colinesterase/farmacologia , Edema/tratamento farmacológico , Antibacterianos/isolamento & purificação , Bacillus cereus/efeitos dos fármacos , Brasil , Inibidores da Colinesterase/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Inflamação/tratamento farmacológico , Medicina Tradicional , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
Here, we propose five fullerene (C60) derivatives as new drugs against Alzheimer's disease (AD). These compounds were designed to act as new human acetylcholinesterase (HssAChE) inhibitors by blocking its fasciculin II (FASII) binding site. Docking and molecular dynamic results show that our proposals bind to the HssAChE tunnel entrance, forming stable complex, and further binding free energy calculations suggest that three of the derivatives proposed here could be potent HssAChE inhibitors. We found a region formed by a set of residues (Tyr72, Asp74, Trp286, Gln291, Tyr341, and Pro344) which can be further exploited in the drug design of new inhibitors of HssAChE based on C60 derivatives. Results presented here report for the first time by a new class of molecules that can become effective drugs against AD.
Assuntos
Acetilcolinesterase/química , Fulerenos/química , Modelos Moleculares , Conformação Molecular , Acetilcolinesterase/metabolismo , Sítios de Ligação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Fulerenos/metabolismo , Fulerenos/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação ProteicaRESUMO
Girgensohnine alkaloid was used as a natural model in the design and generation of new alkaloid-like α-aminonitrile series that was completed by the use of SSA-catalyzed Strecker reaction between commercial and inexpensive substituted benzaldehydes, piperidine (pyrrolidine, morpholine and N-methylpiperazine) and acetone cyanohydrin. Calculated ADMETox parameters of the designed analogs revealed their good pharmacokinetic profiles indicating lipophilic characteristics. In vitro AChE enzyme test showed that obtained α-aminonitriles could be considered as AChEIs with micromolar IC50 values ranging from 42.0 to 478.0 µM (10.3-124.0 µg/mL). Among this series, the best AChE inhibitor was the pyrrolidine α-aminonitrile 3 (IC50 = 42 µM), followed by the piperidine α-aminonitriles 2 and 6 (IC50 = 45 µM and IC50 = 51 µM, respectively), and the compound 7 (IC50 = 51 µM). In vivo insecticidal activity of more active AChEIs against Aedes aegypti larvae was also performed showing a good larvicidal activity at concentrations less than 140 ppm, highlighting products 2 and 7 that could serve as lead compounds to develop new potent and selective insecticides.