Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties.
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 alkaloi...
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doaj-784b28c4d84d47b89418853cfbc557ec2020-11-24T21:54:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019847610.1371/journal.pone.0198476Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties.Jefferson A RochaNayra C S RegoBruna T S CarvalhoFrancisco I SilvaJose A SousaRicardo M RamosIonara N G PassosJosué de MoraesJose R S A LeiteFrancisco C A LimaSchistosomiasis 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.http://europepmc.org/articles/PMC6019389?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jefferson A Rocha Nayra C S Rego Bruna T S Carvalho Francisco I Silva Jose A Sousa Ricardo M Ramos Ionara N G Passos Josué de Moraes Jose R S A Leite Francisco C A Lima |
spellingShingle |
Jefferson A Rocha Nayra C S Rego Bruna T S Carvalho Francisco I Silva Jose A Sousa Ricardo M Ramos Ionara N G Passos Josué de Moraes Jose R S A Leite Francisco C A Lima Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. PLoS ONE |
author_facet |
Jefferson A Rocha Nayra C S Rego Bruna T S Carvalho Francisco I Silva Jose A Sousa Ricardo M Ramos Ionara N G Passos Josué de Moraes Jose R S A Leite Francisco C A Lima |
author_sort |
Jefferson A Rocha |
title |
Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. |
title_short |
Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. |
title_full |
Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. |
title_fullStr |
Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. |
title_full_unstemmed |
Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. |
title_sort |
computational quantum chemistry, molecular docking, and admet predictions of imidazole alkaloids of pilocarpus microphyllus with schistosomicidal properties. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2018-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC6019389?pdf=render |
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