Curcumin interferes with chitin synthesis in Aedes aegypti: a computational and experimental investigation

Abstract

Throughout history, vector-borne diseases have consistently posed significant challenges to human health. Among the strategies for vector control, chemical insecticides have seen widespread use since their inception. Nevertheless, their effectiveness is continually undermined by the steady growth of insecticide resistance within these vector populations. As such, the demand for more robust, efficient, and cost-effective natural insecticides has become increasingly pressing. One promising avenue of research focuses on chitin, a crucial structural component of mosquitoes' exoskeletons and other insects. Chitin not only provides protection and rigidity but also lends flexibility to the insect body. It undergoes substantial transformations during insect molting, a process known as ecdysis. Crucially, the production of chitin is facilitated by an enzyme known as chitin synthase, making it an attractive target for potential novel insecticides. Our recent study delved into the impacts of curcumin, a natural derivative of turmeric, on chitin synthesis and larval development in Aedes aegypti, a mosquito species known to transmit dengue and yellow fever. Our findings demonstrate that even sub-lethal amounts of curcumin can significantly reduce overall chitin content and disrupt the cuticle development in the 4th instar larvae of Aedes aegypti. Further to this, we utilized computational analyses to investigate how curcumin interacts with chitin synthase. Techniques such as molecular docking, pharmacophore feature mapping, and molecular dynamics (MD) simulations helped to illustrate that curcumin binds to the same site as polyoxin D, a recognized inhibitor of chitin synthase. These findings point to curcumin's potential as a natural, bioactive larvicide that targets chitin synthase in mosquitoes and potentially other insects.

Graphical abstract