ABSTRACT
Because mosquito control depend on the use of commercial insecticides and resistance has been described in some of them, there is a need to explore new molecules no resistant. In vivo effects of girgensohnine analog 2-(3,4-dimethoxyphenyl)-2-(piperidin-1-yl)acetonitrile DPPA and Cymbopogon flexuosus essential oil CFEO, on the detoxifying enzymes acetylcholinesterase (AChE), glutathione-S-transferase (GST), nonspecific esterases (α- and ß-), mixed function oxidases (MFO) and p-NPA esterases were evaluated on a Rockefeller (Rock) and wild Aedes aegypti population from Santander, Colombia (WSant). The action was tested after 24h of exposure at concentrations of 20.10, 35.18 and 70.35mgL-1 of DPPA and 18.45, 30.75 and 61.50mgL-1 of CFEO, respectively. It was found that AChE activity of Rock and WSant was not influenced by the evaluated concentration of DPPA and CFEO (p>0.05), while MFO activity was significantly affected by all CFEO concentrations in WSant (p<0.05). GST, α- and ß-esterase activities were affected in Rock exposed at the highest CFEO concentration, this concentration also modified ß-esterases activity of WSant. DPPA and CFEO sublethal doses induced inhibition of AChE activity on untreated larvae homogenate from 12 to 20% and 18 to 26%, respectively. For untreated adult homogenate, the inhibition activity raised up to 14 to 27% for DPPA and 26 to 34% for CFEO. Elevated levels of detoxifying enzymes, found when CFEO was evaluated, showed a larval sensitivity not observed by the pure compound suggesting that DPPA, contrary to CFEO, was not recognized, transformed or eliminated by the evaluated detoxifying enzymes.
Subject(s)
Aedes/enzymology , Cymbopogon/chemistry , Nitriles/pharmacology , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Pyrrolidines/pharmacology , Acetylcholinesterase/metabolism , Aedes/drug effects , Animals , Insecticides/chemistry , Insecticides/pharmacology , Larva/drug effects , Larva/enzymology , Mixed Function Oxygenases , Molecular Structure , Nitriles/chemistry , Oils, Volatile/chemistry , Plant Oils/chemistry , Pyrrolidines/chemistryABSTRACT
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.
Subject(s)
Acetylcholinesterase/metabolism , Aedes/chemistry , Cholinesterase Inhibitors/pharmacology , Dengue/drug therapy , Drug Design , Insect Vectors/chemistry , Insecticides/pharmacology , Nitriles/pharmacology , Pyrrolidines/pharmacology , Animals , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Dose-Response Relationship, Drug , Insecticides/chemical synthesis , Insecticides/chemistry , Larva/drug effects , Molecular Structure , Nitriles/chemical synthesis , Nitriles/chemistry , Pyrrolidines/chemical synthesis , Pyrrolidines/chemistry , Structure-Activity RelationshipABSTRACT
The dynamics of the control of Aedes (Stegomyia) aegypti Linnaeus, (Diptera, Culicidae) by Bacillus thuringiensis var israelensis has been related with the temperature, density and concentration of the insecticide. A mathematical model for biological control of Aedes aegypti with Bacillus thuringiensis var israelensis (Bti) was constructed by using data from the literature regarding the biology of the vector. The life cycle was described by differential equations. Lethal concentrations (LC50 and LC95) of Bti were determined in the laboratory under different experimental conditions. Temperature, colony, larvae density and bioinsecticide concentration presented marked differences in the analysis of the whole set of variables; although when analyzed individually, only the temperature and concentration showed changes. The simulations indicated an inverse relationship between temperature and mosquito population, nonetheless, faster growth of populations is reached at higher temperatures. As conclusion, the model suggests the use of integrated control strategies for immature and adult mosquitoes in order to achieve a reduction of Aedes aegypti.
Foi elaborado um modelo matemático do controle biológico de Aedes aegypti com foco em Bacillus thuringiensis var israelensis (Bti). Na construção do modelo foram utilizados dados da literatura sobre a biologia do vetor, no qual o ciclo de vida foi descrito através de equações diferenciais. As concentrações letais (CL50 e CL95) do Bti foram determinadas no laboratório sob diferentes condições experimentais. As variáveis temperatura, colônia, densidade de larvas e concentração do bioinseticida acusaram diferenças significativas quando analisadas no modelo geral, porém quando analisadas individualmente, apenas a temperatura e concentração apresentaram diferenças. As simulações do modelo indicam que a temperatura afeta inversamente a produção de indivíduos e que os pontos máximos de produção de mosquitos são atingidos mais rápido a temperaturas maiores. Concluímos, com a simulação do modelo, que estratégias integradas de controle de imaturos e adultos devem ser utilizadas para atingir redução expressiva da população de Aedes aegypti.
Subject(s)
Animals , Male , Female , Aedes , Insecticides , Models, Theoretical , Pest Control, Biological , Temperature , Population DensityABSTRACT
OBJETIVOS: Se presenta un modelo de simulación que muestra la dinámica de depredación de Mesocyclops spp., sobre Aedes aegypti MÉTODOS: Representado por cuatro ecuaciones diferenciales: H'(t), cantidad de huevos; L'(t), cantidad de larvas; A'(t), cantidad de adultos y C'(t), cantidad de copépodos. Inicialmente las ecuaciones son del tipo clásico presa-depredador, según Lotka y Volterra. Posteriormente se modifica en un sistema con respuesta funcional para invertebrados, según Holling. RESULTADOS: El primer sistema controla y estabiliza la población de mosquitos, el segundo muestra que los copepodos son inefectivos como controladores. CONCLUSIONES: Se reconoce la necesidad de estudiar sistemas presa depredador (mosquitos - copepodos) con trabajos que integren pruebas de laboratorio y de campo. Solo así será posible establecer la validez en el uso de estos últimos como controladores biológicos efectivos de mosquitos.
