Design of Inhibitors Targeting Chitin-Degrading Enzymes by Bioisostere Substitutions and Scaffold Hopping for Selective Control of .

Chitin-degrading enzymes are critical components in regulating the molting process of the Asian corn borer and serve as potential targets for controlling this destructive pest of maize. Here, we used a scaffold-hopping strategy to design a series of efficient naphthylimide insecticides. Among them, compound exhibited potent inhibition of chitinase from Chi-h and ChtI at low nanomolar concentrations (IC = 1.

Design, Synthesis, and Biological Investigations of Novel Carbamoylguanidinyl Nitrobenzoxadiazoles against Chitinolytic Enzymes.

Chitinase has been identified as an important target for insecticides. In this study, a series of novel chitinase inhibitors was designed and synthesized with nitrobenzoxadiazoles. Compound , which contains the -methylcarbamoylguanidinyl, exhibited high enzyme inhibitory activity and achieved nanomolar inhibition against ChtI (IC = 12.

Discovery of Potent -Methylcarbamoylguanidino Insect Growth Regulators Targeting ChtI and Chi-h.

Insect growth regulators (IGRs) are important insecticides that reduce the harm caused by insects to crops by controlling pest population growth. Chitinases are closely associated with insect growth and are among the most important glycoside hydrolases. Thus, Chitinase is an attractive target for the development of novel insecticides.

Application of Natural Bioresources to Sustainable Agriculture: A -Glycoside Insecticide Based on -Acetyl-glucosamine for Regulating Insect Molting of .

In order to increase the application of natural bioresources in drug discovery and development, a study on -acetyl-glucosamine (GlcNAc) derivatives of chitin as green pesticides was necessary. In this study, we designed and synthesized a series of novel glycoside naphthalimides using GlcNAc as a starting material. Compound showed high inhibitory activity against Hex1 (IC = 1.

Discovery of aromatic 2-(3-(methylcarbamoyl) guanidino)-N-aylacetamides as highly potent chitinase inhibitors.

Chitinases are important glycoside hydrolases that are closely related to bacterial pathogenesis, fungal cell wall remodelling, and insect moulting. Consequently, chitinases have become attractive targets for therapeutic drugs and pesticides. In this study, we designed and synthesised a series of novel chitinase inhibitors based on the N-methylcarbamoylguanidinyl group of the natural product argifin.

Rational Design and Identification of Novel Piperine Derivatives as Multichitinase Inhibitors.

Asian corn borer () is one of the most destructive pests in agriculture. Three chitinases ChtI, ChtII, and Chi-h are regarded as potential targets for discovering novel agrochemicals to control . In this study, piperine ( = 43.

Design, synthesis, biologically evaluation and molecular docking of C-glycosidic oximino carbamates as novel OfHex1 inhibitors.

The inhibition of function-specific β-N-acetyl-D-hexosaminidases, such as OfHex1 from the Asian corn borer (Ostrinia furnacalis), is a promising strategy for the development of green pesticides. Among reported OfHex1 inhibitors, glycosyl inhibitors show especially high inhibitory activity. In this study, a series of novel C-glycosidic oximino carbamate derivatives were designed using the OfHex1 crystal structure and synthesized.

Coassembly of a New Insect Cuticular Protein and Chitosan via Liquid-Liquid Phase Separation.

Insect cuticle is a fiber-reinforced composite material that consists of polysaccharide chitin fibers and a protein matrix. The molecular interactions between insect cuticle proteins and chitin that govern the assembly and evolution of cuticles are still not well understood. Herein, we report that cuticular protein hypothetical-1 (CPH-1), a newly discovered and most abundant cuticular protein from Asian corn borer , can form coacervates in the presence of chitosan.

Discovery of Biphenyl-Sulfonamides as Novel β--Acetyl-d-Hexosaminidase Inhibitors via Structure-Based Virtual Screening.

Novel insecticidal targets are always in demand due to the development of resistance. Hex1, a β--acetyl-d-hexosaminidase identified in (Asian corn borer), is involved in insect chitin catabolism and has proven an ideal target for insecticide development. In this study, structure-based virtual screening, structure simplification, and biological evaluation are used to show that compounds with a biphenyl-sulfonamide skeleton have great potential as Hex1 inhibitors.

Fabrication of gelatin microspheres containing ammonium hydrogen carbonate for the tunable release of herbicide.

The major challenge in utilizing pesticides lies in identifying the precise application that would improve the efficiency of these pesticides and decline their environmental and health hazards at the same time. Such application requires the development of specific formulations that enable controlled, stimuli-responsive release of the pesticides. Gelatin is a relatively cheap material characterized by temperature-sensitivity and abundant amino acid groups, which makes it suitable for the storage and controlled release of pesticides.

Fabrication of Non-phospholipid Liposomal Nanocarrier for Sustained-Release of the Fungicide Cymoxanil.

Liposome nanocarriers can be used to solve problems of pesticide instability, rapid degradation and a short period of efficacy. Cymoxanil with antifungal activity requires an ideal drug loading system due to its degradation issues. In this paper, cholesterol and stearylamine were used to prepare non-phospholipid liposomes (sterosomes) as a pesticide nanocarrier, and were characterized with field emission scanning electron microscopy (FE-SEM), X-ray powder diffraction (XRD), Fourier-transform infrared (FT-IR) spectrometer, size distribution, and ζ-potential.

An overall look at insect chitin deacetylases: Promising molecular targets for developing green pesticides.

Chitin deacetylase (CDA) is a key enzyme involved in the modification of chitin and plays critical roles in molting and pupation, which catalyzes the removal of acetyl groups from -acetyl-D-glucosamine residues in chitin to form chitosan and release acetic acid. Defects in the CDA genes or their expression may lead to stunted insect development and even death. Therefore, CDA can be used as a potential pest control target.

Cloning, expression, and functional analysis of the β-1,3-glucanase gene in Ostrinia furnacalis.

The β-1,3-glucanase gene in Ostrinia furnacalis was first obtained by RT-PCR. The real-time fluorescence quantitative PCR showed that the expression level of β-1,3-glucanase in the midgut of O. furnacalis was higher than in other tissues.

Preparation and characterization of chitosan/Nano-ZnO composite film with antimicrobial activity.

Chitosan is promising material for making food packaging film with antimicrobial activity. However, chitosan film usually has limited mechanical and antimicrobial properties and higher water solubility. To improve the performance of chitosan film, in this work, chitosan composite films were prepared by incorporating different sizes of zinc oxide particles of 5 μm, 100 nm, and 50 nm.

Synthesis of ureido thioglycosides as novel insect β‑N‑acetylhexosaminidase OfHex1 inhibitors.

The insect β-N-acetylhexosaminidase OfHex1 from Ostrinia furnacalis (one of the most destructive agricultural pests) has been considered as a promising pesticide target. In this study, a series of novel and readily available ureido thioglycosides were designed and synthesized based on the catalytic mechanism and the co-crystal structures of OfHex1 with substrates. After evaluation via enzyme inhibition experiments, thioglycosides 11c and 15k were found to have inhibitory activities against OfHex1 with the K values of 25.

Mucin family genes are essential for the growth and development of the migratory locust, Locusta migratoria.

Mucins are highly glycosylated proteins that are characterized by a higher proportion of threonine, serine, and proline residues in their sequences. Although mucins in humans and vertebrates have been implicated in many biological processes, their roles in growth and development in invertebrates such as in insects remain largely unknown. Based on bioinformatic analyses, we identified eight mucin or mucin-like genes in the migratory locust, Locusta migratoria.

Insect group II chitinase OfChtII promotes chitin degradation during larva-pupa molting.

The insect group II chitinase (ChtII, also known as Cht10) is a unique chitinase with multiple catalytic and chitin-binding domains. It has been proven genetically to be an essential chitinase for molting. However, ChtII's role in chitin degradation during insect development remains poorly understood.

Potent Fungal Chitinase for the Bioconversion of Mycelial Waste.

mycelial waste is a good raw material for production of -acetyl-d-glucosamine (GlcNAc). In this study, ChiB, an chitinase which is upregulated during autolysis, was found to degrade mycelial waste with high efficiency. It could produce 1.

Virtual screening, synthesis, and bioactivity evaluation for the discovery of β-N-acetyl-D-hexosaminidase inhibitors.

Background: Molting is an essential insect developmental process, in which a variety of enzymes are involved. The inhibition of these enzymes effect normal insect growth and development and may even cause death. OfHex1, one of the β-N-acetyl-D-hexosaminidases, is a key enzyme involved in the molting process of the Asian corn borer (Ostrinia furnacalis), and is deemed a potential insecticidal target.

Development of Novel Pesticides Targeting Insect Chitinases: A Minireview and Perspective.

Chitinase (EC 3.2.1.

A Series of Compounds Bearing a Dipyrido-Pyrimidine Scaffold Acting as Novel Human and Insect Pest Chitinase Inhibitors.

Chitinases not only play vital roles in the human innate immune system but are also essential for the development of pathogenic fungi and pests. Chitinase inhibitors are efficient tools to investigate the elusive role of human chitinases and to control pathogens and pests. Via hierarchical virtual screening, we have discovered a series of chitinase inhibitors with a novel scaffold that have high inhibitory activities and selectivities against human and insect chitinases.