In Silico Studies on Compounds Derived from Calceolaria: Phenylethanoid Glycosides as Potential Multitarget Inhibitors for the Development of Pesticides

Abstract

An increasing occurrence of resistance in insect pests and high mammal toxicity exhibited by common pesticides increase the need for new alternative molecules. Among these alternatives, bioinsecticides are considered to be environmentally friendly and safer than synthetic insecticides. Particularly, plant extracts have shown great potential in laboratory conditions. However, the lack of studies that confirm their mechanisms of action diminishes their potential applications on a large scale. Previously, we have reported the insect growth regulator and insecticidal activities of secondary metabolites isolated from plants of the Calceolaria genus. Herein, we report an in silico study of compounds isolated from Calceolaria against acetylcholinesterase, prophenoloxidase, and ecdysone receptor. The molecular docking results are consistent with the previously reported experimental results, which were obtained during the bioevaluation of Calceolaria extracts. Among the compounds, phenylethanoid glycosides, such as verbascoside, exhibited good theoretical affinity to all the analyzed targets. In light of these results, we developed an index to evaluate potential multitarget insecticides based on docking scores.

Keywords: Calceolaria; bioinsecticides; molecular docking; multitarget; phenylethanoid glycosides; structure–activity relationship.

Figure 1

Plots of variations along time of Molecular Dynamics (MD) simulations of complexes of 87 with DmAChE (red) and hAChE (blue). (a) The Root Mean Square Deviation (RMSD) of protein backbone; (b) distance of compound 87 to Ser 238 (DmAChE) or Ser 203 (hAChE).

Figure 2

Contour plot correlating PPO, DmAChE, and EcR docking scores. Zones in red-yellow indicate higher affinity to EcR than zones in purple or blue.

Figure 3

Structures of phenylethanoid glycosides (compounds 86–90) which exhibited the highest vMTi and wMTi values.

Figure 4

Comparison of (a) the docked pose of verbascoside (compound 87) and (b) 20-E crystallized in the LBD of EcR (PDB:2R40).

Figure 5

Overlap docking poses of compounds 86 (cyan) and 88 (yellow). Histidine residues of catalytic site are shown in green.

Figure 6

Comparison of the docking poses of compound 87 in DmAChE (a) and hAChE (b). Catalytic residues are colored in yellow and residues at the entrance of the active site in orange. Tyr71/Asp 74 residues, which are different in each enzyme, are colored in green. Key hydrogen bond interaction of verbascoside to Asp 74 is shown in black.