![]() ![]() The equilibrium between trehalose storage and degradation needs to be finely tuned in response to different cellular states. When unicellular organisms are exposed to stress, they adapt by synthesizing huge amounts of trehalose, which contributes to retain cellular integrity by stabilizing protein structures in many different ways. In addition, trehalose can act as a chemical “chaperone” by stabilizing proteins in their native structure and thus preventing cellular damage from inactivation or denaturation caused by stress conditions such as desiccations, dehydration, heat, cold, and damage by oxygen radicals. In yeast and plants, trehalose is a signaling compound able to regulate certain metabolic pathways. Since then, knowledge about the various functions of this simple disaccharide greatly expanded, and it is now evident that trehalose is much more than a simple storage compound, although its exact function in many organisms is still under investigation. In the 1970s, trehalose was merely regarded as a storage form of glucose for energy and/or for cellular components structure. However, trehalose is not found in mammals. This disaccharide is present in a wide variety of organisms, including yeast, fungi, bacteria, insects, some invertebrates, and lower and higher plants. Trehalose ( 1, Figure 1) is a peculiar non-reducing disaccharide featured by the presence of two glucose units linked through an α,α-1,1-glycosidic linkage. The identification of a new target which is specific for insects and does not affect humans is therefore of particular relevance. The development of non-toxic, environmentally friendly insecticides and fungicides for human health and for crop protection is of great interest, especially for less developed countries affected by pandemic and starvation. In September 2006, the World Health Organization (WHO) declared its support for the indoor use of DDT in African countries where malaria remains a major health problem, citing that the benefits of the pesticide outweigh the health and environmental risks. However, DDT is still very efficient against malaria and other diseases caused by insects. For these reasons, the US banned the use of DDT in 1972. DDT is a very toxic and persistent organic compound, its chemical stability provokes a long range transport into the environment and its non-hydrophilicity causes bioaccumulation in the tissues of animals and human beings. In the past, the non-restricted use of highly dangerous insecticides such as dichlorodiphenyltrichloroethane (DDT) has provoked negative effects in the environment and to mammals. ![]() Insecticides and fungicides have played a fundamental role in raising the quality of our lives, not only for crop protection in agriculture, but also to avoid the spreading of harmful pests causing lethal human diseases, such as malaria. The results reported here represent an overview and a discussion of the best candidates which may lead to the development of an effective insecticide in the future. Although natural complex pseudo di- and trisaccharides were firstly studied to this aim, iminosugars look to be more promising, showing an excellent specificity profile towards insect trehalases. Despite their attractiveness as a target, up to now there are no trehalase inhibitors that have been developed as commercial insecticides. ![]() Specifically, we analyzed trehalase inhibitors based on sugars and sugar mimics, focusing on those showing good inhibition properties towards insect trehalases. This review aims to describe the efforts made in the last 50 years in the evaluation of natural compounds and their analogues as trehalase inhibitors, in view of their potential use as insecticides and fungicides. The lesson on this topic that we learned from the past can be of great help in the research on new specific green pesticides. In the era of green economy, trehalase inhibitors represent a valuable chance to develop non-toxic pesticides, being hydrophilic compounds that do not persist in the environment. ![]()
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