studies of benzothiazole derivatives as potential inhibitors of and trehalase.

INTRODUCTION

In malaria management, insecticides play a crucial role in targeting disease vectors. Benzothiazole derivatives have also been reported to possess insecticidal properties, among several other properties they exhibit. The female Anopheles mosquito is responsible for transmitting the malaria parasite when infected. () and () are two of the most notable Anopheles species known to spread malaria in Nigeria. Trehalase is an enzyme that breaks down trehalose. Recent research has proposed it as a viable target for inhibition since it aids in flight and stress adaptation.

METHODS

This study aimed to investigate benzothiazole derivatives as potential inhibitors of trehalase of Anopheles funestus (Tre) and Anopheles gambiae (Tre) using toxicity profiling, molecular docking, and dynamic simulation for future insecticidal intervention. A total of 4,214 benzothiazole-based compounds were obtained from the PubChem database and subjected to screening against the 3D modelled structure of Tre and Tre. Compounds with some toxicity levels were optimised, and the obtained lead compounds were further investigated through molecular docking studies. Furthermore, the best hit was subjected to parameters such as RMSD, RMSF, SASA, Rg, and hydrogen bond to confirm its stability when in a complex with Tre, and these parameters were compared to that of validamycin A (control ligand).

RESULTS AND DISCUSSION

The post-screening analysis showed binding affinities of -8.7 and -8.2 kcal/mol (compound 1), -8.2 and -7.4 kcal/mol (compound 2), compared to -6.3 and -5.1 kcal/mol (Validamycin A, a known inhibitor) against Tre and Tre, respectively. The molecular dynamics simulation showed that compound 1 (the best hit) had good stability when in complex with Tre. These findings suggest that these best hits can serve as potential inhibitors for the development of novel insecticides in the control of malaria vectors.