1. 9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one is a potentially novel antiplatelet drug which antagonizes the effect of thromboxane A2
- Author
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Luciano Saso, Katerina Macáková, Kemal Durić, Lenka Applová, Jana Karlíčková, Elma Veljović, Davorka Završnik, Samija Muratović, and Premysl Mladenka
- Subjects
0301 basic medicine ,030103 biophysics ,Antiplatelet drug ,Stereochemistry ,Thromboxane ,medicine.medical_treatment ,molecular structure ,Pharmacology ,antiplatelet ,dose-response relationship ,03 medical and health sciences ,Thromboxane A2 ,chemistry.chemical_compound ,In vivo ,xanthene-3-one ,Drug Discovery ,medicine ,arachidonic acid ,drug discovery3003 pharmaceutical science ,xanthones ,humans ,platelet aggregation inhibitors ,platelet ,biology ,Dose-Response Relationship, Drug ,structure-activity relationship ,drug ,thromboxane a2 ,cyclooxygenase ,Mechanism of action ,chemistry ,thromboxane ,dose-response relationship, drug ,platelet aggregation ,biology.protein ,Platelet aggregation inhibitor ,Thromboxane-A synthase ,Cyclooxygenase ,medicine.symptom - Abstract
BACKGROUND Currently, used oral antiplatelet drugs are both limited and associated with the risk of treatment failure/resistance. Research in this area is hence highly desired. A series of xanthene-3-ones derivatives, we had synthesized, showed us that these derivatives had antiplatelet activity. As far as we know, no research on the effects of xanthen-3-ones in this area has been done. OBJECTIVE The aim was to study the antiplatelet potential of a series of synthesised 9-phenylxanthene- 3-ones and to find the ideal structural feature(s) for antiplatelet potential and determine the mechanism of action. METHODS The compounds were synthesized from 1,2,4-triacetoxybenzene and various benzaldehydes. The reaction proceeded smoothly under acidic alcoholic conditions, furnishing the desired products in good yields. The compounds were first screened in whole human blood where platelet aggregation was induced by arachidonic acid. Further analysis was targeted at search of the mechanism of action. RESULTS Initial screening showed that a majority of the synthesized derivatives had substantial antiplatelet potential. None of the compounds were able to block cyclooxygenase 1 or thromboxane synthase. The mechanism appeared to be based on antagonism of thromboxane effects. The most potent compound 9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one had better potential to block collagen induced platelet aggregation than clinically used acetylsalicylic acid. CONCLUSION The last mentioned derivative is promising for further in vivo testing.
- Published
- 2018