Exploring the Potentiality of Natural Products from Essential Oils as Inhibitors of Odorant-Binding Proteins: A Structure- and Ligand-Based Virtual Screening Approach To Find Novel Mosquito Repellents

Abstract

Odorant-binding proteins (OBPs) are the main olfactory proteins of mosquitoes, and their structures have been widely explored to develop new repellents. In the present study, we combined ligand- and structure-based virtual screening approaches using as a starting point 1633 compounds from 71 botanical families obtained from the Essential Oil Database (EssOilDB). Using as reference the crystallographic structure of N,N-diethyl-meta-toluamide interacting with the OBP1 homodimer of Anopheles gambiae (AgamOBP1), we performed a structural and pharmacophoric similarity search to select potential natural products from the library. Thymol acetate, 4-(4-methyl phenyl)-pentanal, thymyl isovalerate, and p-cymen-8-yl demonstrated a favorable chemical correlation with DEET and also had high-affinity interactions with the OBP binding pocket that molecular dynamics simulations showed to be stable. To the best of our knowledge, this is the first study to evaluate on a large scale the potentiality of NPs from essential oils as inhibitors of the mosquito OBP1 using in silico approaches. Our results could facilitate the design of novel repellents with improved selectivity and affinity to the protein binding pocket and can shed light on the mechanism of action of these compounds against insect olfactory recognition.

Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches

“…To estimate the binding affinity (ΔG bind ), we used the molecular mechanics/generalized born surface area (MM-GBSA) methods [ 77 , 78 , 79 , 80 ]. The ΔG bind was calculated according to the following equations: ΔG bind = ΔG complex − ΔG receptor − ΔG ligand ΔG bind = ΔH − TΔS ≈ ΔE MM + ΔG solv − TΔS ΔE MM = ΔE internal + ΔE ele + ΔE vdW ΔG solv = ΔG GB + ΔG NP .…”

Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications

“…The compounds from EO described with antioxidant activity represent a relevant fraction of their chemical composition [ 46 ]. These components have been indicated as an interesting source for the development and discovery of new bioactive compounds with pharmaceutical and cosmetic application due to their anti-inflammatory [ 47 ], antibacterial [ 48 ], antifungal [ 49 , 50 ], repellent [ 51 , 52 ], antioxidant [ 53 , 54 , 55 ], and neuroprotective [ 56 ] properties, as well as cytotoxic activities against cancer cell lines [ 57 , 58 ]. In addition, EOs and their constituents have been investigated as an alternative additive in the food industry [ 44 , 59 ] in contrast to synthetic antioxidants, such as butylated hydroxytoluene, butylated hydroxyanisole, and propyl gallate, that have exhibited undesired effects to human health [ 60 , 61 ].…”

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach

“…The initial structure for the system was obtained from molecular docking methods, as described in the previous section. The restrained electrostatic potential (RESP) protocol with the HF/6-31G* basis sets was applied to obtain the charges of the atoms of each ligand [ 106 , 107 , 108 ] Atomic charge calculated using Gaussian [ 81 , 109 , 110 ] The parameters of the ligand were constructed with the Antechamber module, available in the Amber16 package [ 111 , 112 , 113 ]. The protonation state of ionizable residues of protein structure was analyzed using the PROPKA [ 114 ] server in the neutral pH before performing the MD simulations.…”