Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties

Abstract

Schistosomiasis affects million people and its control is widely dependent on a single drug, praziquantel. Computational chemistry has led to the development of new tools that predict molecular properties related to pharmacological potential. We conducted a theoretical study of the imizadole alkaloids of Pilocarpus microphyllus (Rutaceae) with schistosomicidal properties. The molecules of epiisopiloturine, epiisopilosine, isopilosine, pilosine, and macaubine were evaluated using theory models (B3lyp/SDD, B3lyp/6-31+G(d,p), B3lyp/6-311++G(d,p)). Absorption, distribution, metabolization, excretion, and toxicity (ADMET) predictions were used to determine the pharmacokinetic and pharmacodynamic properties of the alkaloids. After optimization, the molecules were submitted to molecular docking calculations with the purine nucleoside phosphorylase, thioredoxin glutathione reductase, methylthioadenosine phosphorylase, arginase, uridine phosphorylase, Cathepsin B1 and histone deacetylase 8 enzymes, which are possible targets of Schistosoma mansoni. The results showed that B3lyp/6-311++G(d,p) was the optimal model to describe the properties studied. Thermodynamic analysis showed that epiisopiloturine and epiisopilosine were the most stable isomers; however, the epiisopilosine ligand achieved a superior interaction with the enzymes studied in the molecular docking experiments, which corroborated the results of previous experimental studies on schistosomiasis.

In silico study of the interactions of Pilocarpus microphyllus imidazolic alkaloids with the main protease (Mpro) of SARS-CoV-2

“…In this study, it is possible to detect the existence of four isomeric forms (C 16 H 18 N 2 O 3 ) for the alkaloids EPR ( Figure 1 a), EPS ( Figure 1 b), IPS ( Figure 1 c) and PS ( Figure 1 d). The presence of optical isomerism in the EPS, IPS and PS molecules is perceived, according to the results of Rocha et al [ 20 ], observed through the rotation of two conforming atoms (C4 and C9), and by the presence of three chiral carbons (C5, C7, and C8), which corroborate with the data presented in the experimental studies of Rocha et al [ 23 ].…”

“…In order to obtain the global minimum energies, thermodynamic properties, Molecular Electrostatic Potential Surface (MEPS), frontier molecular orbitals and descriptors of the global chemical reactivity of the ligands, calculations geometric optimisation and frequency in the gas phase (vacuum system) were performed, at the level of Density Functional Theory (DFT) and based on studies by Rocha et al [ 20 ] and Costa et al [ 32 , 33 ]. For this purpose, it was used the Gaussian 09 software [ 34 ] and the B3LYP hybrid method [ 35 , 36 ] associated with the basis set 6-311++G(d,p) [ 37 , 38 ].…”

Screening Possible Drug Molecules for Covid-19. The Example of Vanadium (III/IV/V) Complex Molecules with Computational Chemistry and Molecular Docking.

“…Frequency calculations were performed to obtain thermodynamic properties and to verify that each optimization achieved an energy minimum. The quantum chemical descriptors extracted directly from the ORCA output le were Huckel charge, electronic density, dipole moment, the energy of the highest occupied molecular orbital (HOMO), and the energy of the lowest unoccupied molecular orbital (LUMO) [21,22].…”

In Silico Molecular Docking and Ab initio DFT Studies as a Tool for a Quick Screening on Drug Inhibitors for SARS-Cov-2 RNA-Dependent Polymerase

“…Frequency calculations were performed to obtain thermodynamic properties and to verify that each optimization achieved an energy minimum. The quantum chemical descriptors extracted directly from the ORCA output le were total energy, Mulliken atomic charges, electronic density, dipole moment, Mayer population analysis, the energy of the highest occupied molecular orbital (HOMO), and the energy of the lowest unoccupied molecular orbital (LUMO) [15,16]. The molecular orbitals and the optimized structures taken by AVOGADRO software [17].…”