Centro de Investigaciones en Enfermedades Tropicales - Cintrop. Escuela de Medicina, Departamento de Ciencias Básicas, Universidad Industrial de Santander, Parque Tecnológico y de Investigaciones, Guatiguará Km 2 El Refugio Piedecuesta, Santander, A.A. (P.O. Box) 678 Bucaramanga, Colombia.
Grupo de Sistemas Organizados (GSO), Instituto para el Desarrollo Agroindustrial y de la Salud (IDAS), Universidad Nacional de Río Cuarto, Río Cuarto, Argentina.
Pestic Biochem Physiol. 2024 Jan;198:105721. doi: 10.1016/j.pestbp.2023.105721. Epub 2023 Dec 7.
Developing new pesticides poses a significant challenge in designing next-generation natural insecticides that selectively target specific pharmacological sites while ensuring environmental friendliness. In this study, we aimed to address this challenge by formulating novel natural pesticides derived from secondary plant metabolites, which exhibited potent insecticide activity. Additionally, we tested their effect on mitochondrial enzyme activity and the proteomic profile of Ae. aegypti, a mosquito species responsible for transmitting diseases. Initially, 110 key compounds from essential oils were selected that have been reported with insecticidal properties; then, to ensure safety for mammals were performed in silico analyses for toxicity properties, identifying non-toxic candidates for further investigation. Subsequently, in vivo tests were conducted using these non-toxic compounds, focusing on the mosquito's larval stage. Based on the lethal concentration (LC), the most promising compounds as insecticidal were identified as S-limonene (LC = 6.4 ppm, LC = 17.2 ppm), R-limonene (LC = 9.86 ppm, LC = 27.7 ppm), citronellal (LC = 40.5 ppm, LC = 68.6 ppm), R-carvone (LC = 61.4 ppm, LC = 121 ppm), and S-carvone (LC = 62.5 ppm, LC = 114 ppm). Furthermore, we formulated a mixture of R-limonene, S-carvone, and citronellal with equal proportions of each compound based on their LC. This mixture specifically targeted mitochondrial proteins and demonstrated a higher effect that showed by each compound separately, enhancing the insecticidal activity of each compound. Besides, the proteomic profile revealed the alteration in proteins involved in proliferation processes and detoxification mechanisms in Ae. aegypti. In summary, our study presents a formulation strategy for developing next-generation natural insecticides using secondary plant metabolites with the potential for reducing the adverse effects on humans and the development of chemical resistance in insects. Our findings also highlight the proteomic alteration induced by the formulated insecticide, showing insight into the mechanisms of action and potential targets for further exploration in vector control strategies.
开发新农药在设计下一代天然杀虫剂时带来了重大挑战，需要确保选择性靶向特定药理靶点的同时还具有环境友好性。在这项研究中，我们旨在通过制定新型天然杀虫剂来应对这一挑战，这些杀虫剂源自植物次生代谢产物，具有强大的杀虫剂活性。此外，我们还测试了它们对埃及伊蚊（一种传播疾病的蚊子）线粒体酶活性和蛋白质组谱的影响。首先，从已报道具有杀虫特性的精油中选择了 110 种关键化合物；然后，为确保对哺乳动物的安全性，我们进行了毒性特性的计算机分析，确定了进一步研究的无毒候选物。随后，我们使用这些无毒化合物进行了体内测试，重点关注蚊子的幼虫阶段。根据致死浓度（LC），我们确定了最有前途的作为杀虫剂的化合物为 S-柠檬烯（LC=6.4ppm，LC=17.2ppm）、R-柠檬烯（LC=9.86ppm，LC=27.7ppm）、香茅醛（LC=40.5ppm，LC=68.6ppm）、R-蒈烯（LC=61.4ppm，LC=121ppm）和 S-蒈烯（LC=62.5ppm，LC=114ppm）。此外，我们根据它们的 LC 比例，将 R-柠檬烯、S-蒈烯和香茅醛混合在一起，形成了一种混合物。这种混合物专门针对线粒体蛋白，表现出比每个化合物单独作用更高的效果，从而增强了每个化合物的杀虫活性。此外，蛋白质组谱揭示了埃及伊蚊中参与增殖过程和解毒机制的蛋白质的变化。总之，我们的研究提出了一种使用植物次生代谢产物开发下一代天然杀虫剂的配方策略，具有降低对人类的不利影响和减少昆虫对化学物质产生抗性的潜力。我们的研究结果还突出了配方杀虫剂引起的蛋白质组改变，为进一步探索载体控制策略中的作用机制和潜在靶标提供了深入了解。
