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BioMed Research International
Volume 2015 (2015), Article ID 630482, 11 pages
http://dx.doi.org/10.1155/2015/630482
Research Article

Polysulfated Trehalose as a Novel Anticoagulant Agent with Dual Mode of Action

1Protein Conformation and Enzymology Lab, Department of Bio-Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi 110 025, India
2Medicinal Chemistry Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110 025, India
3Defense Institute of Physiology & Allied Sciences, Timarpur, Delhi 110 054, India

Received 30 May 2014; Revised 26 August 2014; Accepted 28 August 2014

Academic Editor: Helen Mani

Copyright © 2015 Qudsia Rashid et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Physiological hemostatic balance is a coordinated outcome of counteracting coagulation and fibrinolytic systems. An imbalance of procoagulant and anticoagulant factors may result in life threatening thromboembolism. Presently, anticoagulant administration is the first line of therapy for the treatment of these conditions and several anticoagulants have been approved, including various forms of heparin. However, the polyanionic nature and multispecificity of heparin pose several complications. Generally, the polysulfated compounds with antithrombotic potential are thought to have feasible synthetic procedures with much less bleeding, thus having favourable safety profiles. Here we report the synthesis of a novel compound, trehalose octasulfate and the assessment of its anticoagulation potential. Molecular docking of trehalose and trehalose octasulfate with antithrombin showed a specificity switch in binding affinity on sulfation, where trehalose octasulfate interacts with critical residues of AT that are either directly involved in heparin binding or in the conformational rearrangement of AT on heparin binding. An in vitro analysis of trehalose octasulfate demonstrated prolonged clotting time. Lead compound when intravenously injected in occlusion induced thrombotic rats showed remarkable reduction in the size and weight of the clot at a low dose. Delay in coagulation time was observed by analysing blood plasma isolated from rats preinjected with trehalose octasulfate. A decrease in Adenosine 5′-Diphosphate (ADP) induced platelet aggregation indicated a probable dual anticoagulant and antiplatelet mechanism of action. To summarize, this study presents trehalose octasulfate as a novel, effective, dual acting antithrombotic agent.