Kaur, H and Singh, S and Kathott Prakash, S and Rode, S and Lonare, S and Kumar, R and Kumar, P and Kumar Sharma, A and Ramamurthy, PC and Singh, J and Khan, NA (2024) Identification and biophysical characterization of potential phytochemical inhibitors of carboxyl/choline esterase from Helicoverpa armigera for advancing integrated pest management strategies. In: Scientific Reports, 14 (1).
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Abstract
In the realm of disease vectors and agricultural pest management, insecticides play a crucial role in preserving global health and ensuring food security. The pervasive use, particularly of organophosphates (OPs), has given rise to a substantial challenge in the form of insecticide resistance. Carboxylesterases emerge as key contributors to OP resistance, owing to their ability to sequester or hydrolyze these chemicals. Consequently, carboxylesterase enzymes become attractive targets for the development of novel insecticides. Inhibiting these enzymes holds the potential to restore the efficacy of OPs against which resistance has developed. This study aimed to screen the FooDB library to identify potent inhibitory compounds targeting carboxylesterase, Ha006a from the agricultural pest Helicoverpa armigera. The ultimate objective is to develop effective interventions for pest control. The compounds with the highest scores underwent evaluation through docking studies and pharmacophore analysis. Among them, four phytochemicals�donepezil, protopine, 3�,4�,5,7-tetramethoxyflavone, and piperine�demonstrated favorable binding affinity. The Ha006a-ligand complexes were subsequently validated through molecular dynamics simulations. Biochemical analysis, encompassing determination of IC50 values, complemented by analysis of thermostability through Differential Scanning Calorimetry and interaction kinetics through Isothermal Titration Calorimetry was conducted. This study comprehensively characterizes Ha006a-ligand complexes through bioinformatics, biochemical, and biophysical methods. This investigation highlights 3�,4�,5,7-tetramethoxyflavone as the most effective inhibitor, suggesting its potential for synergistic testing with OPs. Consequently, these inhibitors offer a promising solution to OP resistance and address environmental concerns associated with excessive insecticide usage, enabling a significant reduction in their overuse. © The Author(s) 2024.
| Item Type: | Journal Article |
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| Publication: | Scientific Reports |
| Publisher: | Nature Research |
| Additional Information: | The copyright for this article belongs to the authors. |
| Keywords: | carboxylesterase; cholinesterase inhibitor; insecticide; phytochemical, animal; chemistry; drug effect; enzymology; Helicoverpa armigera; insecticide resistance; metabolism; molecular docking; molecular dynamics; moth; pest control; procedures, Animals; Carboxylesterase; Carboxylic Ester Hydrolases; Cholinesterase Inhibitors; Helicoverpa armigera; Insecticide Resistance; Insecticides; Molecular Docking Simulation; Molecular Dynamics Simulation; Moths; Pest Control; Phytochemicals |
| Department/Centre: | Division of Interdisciplinary Sciences > Interdisciplinary Centre for Water Research |
| Date Deposited: | 15 Oct 2024 17:17 |
| Last Modified: | 15 Oct 2024 17:17 |
| URI: | http://eprints.iisc.ac.in/id/eprint/86322 |
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