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

Autor(es)

Rocha, Jefferson A. ^{[1, 2, 3]} ; Rego, Nayra C. S. ^{[1, 3]} ; Carvalho, Bruna T. S. ^[1] ; Silva, I, Francisco ; Sousa, Jose A. ^[4] ; Ramos, Ricardo M. ^[5] ; Passos, Ionara N. G. ^[2] ; de Moraes, Josue ^[6] ; Leite, Jose R. S. A. ^[7] ; Lima, Francisco C. A. ^{[4, 3]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Piaui, Res Grp Computat Quantum Chem & Pharmaceut Planni, GPQQ&PF UESPI, Teresina, PI - Brazil

^[2] Univ Fed Maranhao, CIENATEC UFMA, Res Grp Nat Sci & Biotechnol, Grajau, MA - Brazil

^[3] RENORBIO, Focal Point UFPI, Postgrad Program Northeast Network Biotechnol, Teresina, Piaui - Brazil

^[4] Silva, Francisco, I, Univ Estadual Piaui, Res Grp Computat Quantum Chem & Pharmaceut Planni, GPQQ&PF UESPI, Teresina, PI - Brazil

^[5] Fed Inst Piaui, Res Lab Informat Syst, Dept Informat Environm Hlth & Food Prod, LAPESI IFPI, Teresina, PI - Brazil

^[6] Univ Guarulhos, NPDN UNG, Res Ctr Neglected Dis, Guarulhos, SP - Brazil

^[7] Univ Brasilia, UnB, Area Morphol, Fac Med, Campus Darcy Ribeiro, Brasilia, DF - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 13, n. 6 JUN 26 2018.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 16/22488-3 - Reposicionamento de fármacos para doenças negligenciadas: identificação de novos agentes anti-helmínticos
• Beneficiário: Josué de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular