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.

Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria Vector Anopheles arabiensis, In Silico ADMET Prediction and Molecular Target Investigation

“…For instance, larvicidal inhibitors have the ability to bind to sterol carrier protein-2 [56], juvenile hormone-binding protein [57], D7r4 a salivary biogenic amine-binding protein [58], calcium-dependent protein kinase-1 [59], or purine nucleoside phosphorylase targets [60]. The binding investigation of the dihydroquinazolines against the above-mentioned molecular targets allowed us to identify AChE as the most plausible molecular target which corroborated with the predicted brain cell permeability [51][52][53][54][55][56][57][58][59][60]. No crystal structures of Anopheles arabienesis AChE from mosquito are deposited in the Protein Data Bank (PDB) so far.…”

“…On the basis of the preliminary structure-activity relationship of the 2,3-dihydroquinazolin-4(1H)-one derivatives, we explored a variety of enzyme molecular targets in an attempt to identify the mode of action via which the compounds exert their larvicidal effect. It is well known that AChE represents the main molecular target of insecticides [51][52][53][54][55] and can be associated with the larvicidal action of our compounds. However, some insecticide enzyme targets other than AChE were reported.…”

Chemistry, Biological Activities and In Silico Bioprospection of Sterols and Triterpenes from Mexican Columnar Cactaceae

“…These compounds possess a particular type of triterpene skeleton, called pachanane, characterized by the presence of five six-membered rings, and the position of the 27α-CH3 attached to C-15 [96,97]. Pachanol A R1 = -, R2 = H, R3 = CH3; △ 12(13), 14 (15) Pachanol B R1 = H, R2 = -, R3 = αCH3; △ 11(12), 13 (18) Pachanol C Pachanol D Although only Mexican columnar cacti were considered to the construction of the present review, a special mention is necessary to describe the triterpene content of Trichocereus pachanoi, a cactus plant from South America, which is an important source of some compounds named pachanols A-D ( Table 7). These compounds possess a particular type of triterpene skeleton, called pachanane, characterized by the presence of five six-membered rings, and the position of the 27α-CH 3 attached to C-15 [96,97].…”

“…These compounds possess a particular type of triterpene skeleton, called pachanane, characterized by the presence of five six-membered rings, and the position of the 27α-CH3 attached to C-15 [96,97]. Pachanol A R1 = -, R2 = H, R3 = CH3; △ 12(13), 14 (15) Pachanol B R1 = H, R2 = -, R3 = αCH3; △ 11(12), 13 (18) Pachanol C Pachanol D…”

A Definition of “Multitargeticity”: Identifying Potential Multitarget and Selective Ligands Through a Vector Analysis

“…Construction of a multitarget parameter should not be based only on the simple average of the in silico or experimental data; for example, highly selective ligands to a single target would appear as multitarget drugs, since the average is a measure sensitive to extreme values. With this in mind, our research group suggested the use of a virtual multitarget parameter, which consisted of a weighted average of the docking scores of potential biopesticides (Loza-Mejía et al, 2018). This analysis proved useful for comparing a ligand's "multitargeticity."…”