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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-03-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1660-3397/15/3/79 |
| _version_ | 1811307425794359296 |
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| author | Rebeca Cristina Costa Pereira André Luiz Lourenço Luciana Terra Paula Alvarez Abreu Valéria Laneuville Teixeira Helena Carla Castro |
| author_facet | Rebeca Cristina Costa Pereira André Luiz Lourenço Luciana Terra Paula Alvarez Abreu Valéria Laneuville Teixeira Helena Carla Castro |
| author_sort | Rebeca Cristina Costa Pereira |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T09:04:09Z |
| format | Article |
| id | doaj.art-45678a6133e14bde8ce80d276f1cba99 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T09:04:09Z |
| publishDate | 2017-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-45678a6133e14bde8ce80d276f1cba992022-12-22T02:53:02ZengMDPI AGMarine Drugs1660-33972017-03-011537910.3390/md15030079md15030079Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an AntithromboticRebeca Cristina Costa Pereira0André Luiz Lourenço1Luciana Terra2Paula Alvarez Abreu3Valéria Laneuville Teixeira4Helena Carla Castro5Programa de Pós-Graduação em Ciências e Biotecnologia (PPBI), Instituto de Biologia, Universidade Federal Fluminense, Niterói 24210-130, RJ, BrazilLaboratório de Trombose e Câncer, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21944-970, RJ, BrazilPrograma de Pós-Graduação em Ciências e Biotecnologia (PPBI), Instituto de Biologia, Universidade Federal Fluminense, Niterói 24210-130, RJ, BrazilLaboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas—LAMCIFAR, NUPEM, Universidade Federal do Rio de Janeiro, Campus Macaé, Rio de Janeiro27965-045, RJ, BrazilPrograma de Pós-Graduação em Ciências e Biotecnologia (PPBI), Instituto de Biologia, Universidade Federal Fluminense, Niterói 24210-130, RJ, BrazilPrograma de Pós-Graduação em Ciências e Biotecnologia (PPBI), Instituto de Biologia, Universidade Federal Fluminense, Niterói 24210-130, RJ, BrazilThrombosis 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.http://www.mdpi.com/1660-3397/15/3/79marine productsmolecular dockingditerpenesDictyota menstrualisanticoagulantantithrombotic |
| spellingShingle | Rebeca Cristina Costa Pereira André Luiz Lourenço Luciana Terra Paula Alvarez Abreu Valéria Laneuville Teixeira Helena Carla Castro Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic Marine Drugs marine products molecular docking diterpenes Dictyota menstrualis anticoagulant 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 | marine products molecular docking diterpenes Dictyota menstrualis anticoagulant antithrombotic |
| url | http://www.mdpi.com/1660-3397/15/3/79 |
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