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Identification of a new series of carbohydrate-substituted triazoles derivatives presenting antiplatelet activity
Lustosa M.¹ ; De Souza A.M.T.4 ; Loureiro N.I.V.1; Rodrigues C.R.2 ; Albuquerque M.G.3; Silva, F. C.4 ; Souza M.C.B.V.4 ; Ferreira V.F.4 ; Castro H.C.¹
¹LaBioMol, Departamento de Biologia Celular e Molecular, Instituto de Biologia, UFF-RJ; 2ModMolQSAR, Faculdade de Farmácia, UFRJ-RJ; 3LabMMol, Departamento de Química Orgânica, Instituto de Química, UFRJ-RJ; 4PGQO, Departamento de Química Orgânica, Instituto de Química, UFF-RJ.
Purpose: Thrombosis is a pathology that involves coagulation (Deep Venous Thrombosis) and platelet aggregation (Arterial Thrombosis). These thromboembolic diseases are dramatic factors of morbidity and mortality. An effective way to prevent thrombotic events is the anti aggregant therapy as aspirin (ASA). However, a number of evidence indicates that this chronic antiplatelet therapy is frequently associated with gastro-intestinal adverse side effects. Furthermore, the search for innovative and safer antithrombotic drugs than those currently adopted still remains. Literature shows that triazoles present several applications in biological and medical areas against many diseases like cancer, AIDS, Parkinson and Alzheimer. In order to provide a useful guideline for designing more potent compounds against thrombosis and in attempt to elucidate the importance of the triazoles moiety in the structure-activity relationships (SAR), we synthesized and tested two triazoles compounds and seven different carbohydrate-substituted triazoles. Methods: The aggregation assays were carried out using citrate platelet-rich rabbit plasma and Collagen (5µg/mL), ADP (5µM) and Arachidonic acid (100µM) as inducers and seven triazoles derivatives as possible new antiplatelet compounds. Results: Our assays showed that the non-substituted triazoles derivatives didn't show a significant antiplatelet activity. Interestingly, two triazoles carbohydrate-substituted derivatives presenting fructose and xilose moiety, demonstrated an important antiplatelet profile (100% and 80% respectively). These results suggest that the carbohydrate substituent is important for the antiplatelet activity of these compounds when collagen is used as inducer. Since now only collagen-induced platelet aggregation tests were done. In addition, tests with arachidonic acid and ADP are in progress. Conclusion: Briefly, our results suggested that triazoles groups are important when platelet aggregation is induced by collagen. Although, addition of a carbohydrate-substituent increases activity. Supported by: FAPERJ, CNPq and UFF.
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