Molecular Docking of Nimbolide Extracted from Leaves of Azadirachta indica with Protein Targets to Confirm the Antifungal, Antibacterial and Insecticidal Activity.

UNLABELLED: Nimbolide, a tetranortriterpenoid (limonoid) compound isolated from the leaves of Azadirachta indica , was screened both in vitro and in silico for its antimicrobial activity against Fusarium oxysporum f. sp. cubense , Macrophomina phaseolina , Pythium aphanidermatum , Xanthomonas oryzae pv. oryzae, and insecticidal activity against Plutella xylostella . Nimbolide exhibited a concentration-dependent, broad spectrum of antimicrobial and insecticidal activity. P. aphanidermatum (82.77%) was more highly inhibited than F. oxysporum f. sp. cubense (64.46%) and M. phaseolina (43.33%). The bacterium X. oryzae pv. oryzae forms an inhibition zone of about 20.20 mm, and P. xylostella showed about 66.66% mortality against nimbolide. The affinity of nimbolide for different protein targets in bacteria, fungi, and insects was validated by in silico approaches. The 3D structure of chosen protein molecules was built by homology modelling in the SWISS-MODEL server, and molecular docking was performed with the SwissDock server. Docking of homology-modelled protein structures shows most of the chosen target proteins have a higher affinity for the furan ring of nimbolide. Additionally, the stability of the best-docked protein-ligand complex was confirmed using molecular dynamic simulation. Thus, the present in vitro and in silico studies confirm the bioactivity of nimbolide and provide a strong basis for the formulation of nimbolide-based biological pesticides.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-023-01104-6.