Modelling the Anti-Methicillin-Resistant Staphylococcus Aureus (MRSA) Activity of Cannabinoids: A QSAR and Docking Study

Abstract

Twenty-four cannabinoids active against MRSA SA1199B and XU212 were optimized at WB97XD/6-31G(d,p), and several molecular descriptors were obtained. Using a multiple linear regression method, several mathematical models with statistical significance were obtained. The robustness of the models was validated, employing the leave-one-out cross-validation and Y-scrambling methods. The entire data set was docked against penicillin-binding protein, iso-tyrosyl tRNA synthetase, and DNA gyrase. The most active cannabinoids had high affinity to penicillin-binding protein (PBP), whereas the least active compounds had low affinities for all of the targets. Among the cannabinoid compounds, Cannabinoid 2 was highlighted due to its suitable combination of both antimicrobial activity and higher scoring values against the selected target; therefore, its docking performance was compared to that of oxacillin, a commercial PBP inhibitor. The 2D figures reveal that both compounds hit the protein in the active site with a similar type of molecular interaction, where the hydroxyl groups in the aromatic ring of cannabinoids play a pivotal role in the biological activity. These results provide some evidence that the anti-Staphylococcus aureus activity of these cannabinoids may be related to the inhibition of the PBP protein; besides, the robustness of the models along with the docking and Quantitative Structure–Activity Relationship (QSAR) results allow the proposal of three new compounds; the predicted activity combined with the scoring values against PBP should encourage future synthesis and experimental testing.

Predicting the Adsorption of Amoxicillin and Ibuprofen on Chitosan and Graphene Oxide Materials: A Density Functional Theory Study

“…As it can be noted, amoxicillin has the HOMO and LUMO located at different regions in the molecular structure. This behaviour in the frontier orbitals has already been reported before for antimicrobial [91,92], antimicrobial-like [93], and antiprotozoal compounds [94], asserting to be a fundamental molecular characteristic for antimicrobial activity.…”

In Silico Screening of the DrugBank Database to Search for Possible Drugs against SARS-CoV-2

“…In the last twenty years, the frontier orbitals began to play a pivotal role in the medicinal chemistry field; the studies of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) have allowed the understanding of several biological activities, such as antimicrobial [ 62 , 63 , 64 , 65 ], anticancer [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ], antifungal [ 74 , 75 , 76 ], and cytotoxicity [ 77 , 78 , 79 , 80 ]. More recently, the shape of frontier orbitals has been used to differentiate between active and inactive compounds against a specific disease [ 81 , 82 ].…”

“…The main purpose of this section was to investigate whether or not the frontier orbitals shapes could allow qualitatively distinguishing structures with high vs. low anti-COVID-19 activity. For this purpose, the selected structures were optimized at the DFT theory level with the WB97XD/6-311G(d,p) [ 82 , 93 , 111 , 112 ] method, implemented in Gaussian 16 [ 113 ] for Linux. Following optimization, the .chks files were retrieved and used to generate the frontier molecular orbitals with a 0.02 au isosurface.…”

Predictive Quantitative Structure–Activity Relationship Modeling of the Antifungal and Antibiotic Properties of Triazolothiadiazine Compounds

“…The minimum inhibitory concentration of Staphylococcus aureus by the compounds is explained by electronegativities and the HOMO energy descriptors. Electronic properties, including electronegativities, have been shown to be related to anti- Staphylococcus aureus activity by cannabinoids [ 35 ]. Inhibition of the growth of Gram-positive Bacillus subtilis by the compounds is associated with van der Waals forces, electronegativities, and bandgap energy.…”