Mota Tiago F, Silva Caliene M de A, Conceição Maurício Dos S, Fraga Deborah B M, Brodskyn Claudia I, Neto Moysés F de A, Santana Isis B, Mesquita Paulo R R, Leite Franco H A, Magalhães-Júnior Jairo T
Laboratório de Interação Parasito-Hospedeiro e Epidemiologia (LaIPHE), Instituto Gonçalo Moniz (IGM), FIOCRUZ-BA, Rua Waldemar Falcão, 121 Candeal, 40296-710, Salvador, Bahia, Brazil.
Centro Multidisciplinar do Campus de Barra da Universidade Federal do Oeste da Bahia, Bahia, Brasil.
Acta Trop. 2022 May;229:106367. doi: 10.1016/j.actatropica.2022.106367. Epub 2022 Feb 12.
In the Americas, Lutzomyia longipalpis is the most relevant sand fly species for the transmission of visceral leishmaniasis. For its vector control in Brazil, insecticide spraying has not shown persistent reduction in disease prevalence while some sand fly populations are reported resistant to the insecticides used in spraying. The usage of repellents and personal protection behavior can reduce vector borne diseases prevalence. Therefore, the search for new repellent compounds is needed to use together with insecticide spraying, especially from natural sources to overcome the resistance developed by some sand fly populations to the compounds commercially used. In silico strategies have been applied together with repellency bioassays successfully identifying new bioactive compounds from natural sources. Thus, the present study aimed to screen repellent potential of neem (Azadirachta indica), citronella (Cymbopogon winterianus), bushy matgrass (Lippia alba) and 'alecrim do mato' (Lippia thymoides) essential oils against L. longipalpis and to identify potential repellent compounds by chemical analysis and in silico approach. Plant essential oils were extracted from leaves and repellency bioassays were performed on volunteers using colony reared L. longipalpis. Aside from neem oil, all other tested essential oil has shown a reduced number of sand fly bites using higher concentrations. Chemical composition from oils was assessed and its compounds were screened on a pharmacophore model using odorant binding protein 1 (OBP1). All essential oils were majorly composed of either oxygenated monoterpenes, except for the oil extracted from neem which was composed of sesquiterpene hydrocarbons. Molecular docking was performed with the compounds that best superimposed in the OBP1 pharmacophore model, identifying those binding to OBP4, which is associated with insect repellency behavior. Citronellol, Citronellol acetate, Citronellal and Geranyl acetate showed similar interactions with OBP4 binding site as DEET. Thus, it is suggested that these compounds are able to bind to L. longipalpis OBP4 generating repellent behavior in sand flies.
在美洲，长须罗蛉是内脏利什曼病传播中最相关的白蛉物种。在巴西对其进行病媒控制时，喷洒杀虫剂并未使疾病流行率持续降低，同时有报道称一些白蛉种群对喷洒所用的杀虫剂具有抗性。使用驱虫剂和个人防护行为可降低病媒传播疾病的流行率。因此，需要寻找新的驱虫化合物与杀虫剂喷洒联合使用，尤其是来自天然来源的化合物，以克服一些白蛉种群对商业使用化合物产生的抗性。计算机模拟策略已与驱避生物测定法一起成功应用，从天然来源中鉴定出新的生物活性化合物。因此，本研究旨在筛选印楝（印楝）、香茅（香茅）、多枝假马鞭（白花假马鞭）和“alecrim do mato”（百里香叶假马鞭）精油对长须罗蛉的驱避潜力，并通过化学分析和计算机模拟方法鉴定潜在的驱避化合物。从叶片中提取植物精油，并使用实验室饲养的长须罗蛉对志愿者进行驱避生物测定。除印楝油外，所有其他测试精油在较高浓度下均显示白蛉叮咬数量减少。评估了精油的化学成分，并使用气味结合蛋白1（OBP1）在药效团模型上筛选其化合物。所有精油主要由含氧单萜组成，除了从印楝中提取的精油由倍半萜烃组成。对在OBP1药效团模型中最佳叠加的化合物进行分子对接，鉴定出与OBP4结合的化合物，OBP4与昆虫驱避行为相关。香茅醇、乙酸香茅酯、香茅醛和乙酸香叶酯与OBP4结合位点的相互作用与避蚊胺相似。因此，建议这些化合物能够与长须罗蛉OBP4结合，在白蛉中产生驱避行为。
