Journal
MARINE DRUGS
Volume 15, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/md15030079
Keywords
marine products; molecular docking; diterpenes; Dictyota menstrualis; anticoagulant; antithrombotic
Categories
Funding
- FAPERJ (Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro)
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
- PROPPI-UFF (Pro-Reitoria de Pesquisa, Pos-Graduacao e Inovacao-Universidade Federal Fluminense)
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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.
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