Cargando…

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydict...

Descripción completa

Detalles Bibliográficos
Autores principales: Pereira, Rebeca Cristina Costa, Lourenço, André Luiz, Terra, Luciana, Abreu, Paula Alvarez, Laneuville Teixeira, Valéria, Castro, Helena Carla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367036/
https://www.ncbi.nlm.nih.gov/pubmed/28335516
http://dx.doi.org/10.3390/md15030079
_version_ 1782517702153207808
author Pereira, Rebeca Cristina Costa
Lourenço, André Luiz
Terra, Luciana
Abreu, Paula Alvarez
Laneuville Teixeira, Valéria
Castro, Helena Carla
author_facet Pereira, Rebeca Cristina Costa
Lourenço, André Luiz
Terra, Luciana
Abreu, Paula Alvarez
Laneuville Teixeira, Valéria
Castro, Helena Carla
author_sort Pereira, Rebeca Cristina Costa
collection PubMed
description Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60), which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents.
format Online
Article
Text
id pubmed-5367036
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-53670362017-03-31 Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic Pereira, Rebeca Cristina Costa Lourenço, André Luiz Terra, Luciana Abreu, Paula Alvarez Laneuville Teixeira, Valéria Castro, Helena Carla Mar Drugs Article Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60), which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents. MDPI 2017-03-20 /pmc/articles/PMC5367036/ /pubmed/28335516 http://dx.doi.org/10.3390/md15030079 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pereira, Rebeca Cristina Costa
Lourenço, André Luiz
Terra, Luciana
Abreu, Paula Alvarez
Laneuville Teixeira, Valéria
Castro, Helena Carla
Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic
title Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic
title_full Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic
title_fullStr Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic
title_full_unstemmed Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic
title_short Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic
title_sort marine diterpenes: molecular modeling of thrombin inhibitors with potential biotechnological application as an antithrombotic
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367036/
https://www.ncbi.nlm.nih.gov/pubmed/28335516
http://dx.doi.org/10.3390/md15030079
work_keys_str_mv AT pereirarebecacristinacosta marinediterpenesmolecularmodelingofthrombininhibitorswithpotentialbiotechnologicalapplicationasanantithrombotic
AT lourencoandreluiz marinediterpenesmolecularmodelingofthrombininhibitorswithpotentialbiotechnologicalapplicationasanantithrombotic
AT terraluciana marinediterpenesmolecularmodelingofthrombininhibitorswithpotentialbiotechnologicalapplicationasanantithrombotic
AT abreupaulaalvarez marinediterpenesmolecularmodelingofthrombininhibitorswithpotentialbiotechnologicalapplicationasanantithrombotic
AT laneuvilleteixeiravaleria marinediterpenesmolecularmodelingofthrombininhibitorswithpotentialbiotechnologicalapplicationasanantithrombotic
AT castrohelenacarla marinediterpenesmolecularmodelingofthrombininhibitorswithpotentialbiotechnologicalapplicationasanantithrombotic