The interest towards coumarin-based structures stems from their polypharmacological profile. Herein, we present a series of Mannich bases and 7-azomethine-linked coumarin derivatives exhibiting antiplatelet and antithrombotic activities, in addition to the already known anti-inflammatory and antioxidant activities. Among others, compounds 15 and 16 were found to be the most potent and selective inhibitors of platelet aggregation whereas compound 3 also proved to be the most potent in the clot retraction assay. Structure-activity relationship studies were conducted to elucidate the molecular determinants responsible for the herein observed activities. The chance of inhibiting cyclooxygenase-1 was also investigated for evaluating the platelet aggregation induced by arachidonic acid. Taken together, these results suggest that the investigation of other targets connected to the antiplatelet activity, such as phosphodiesterase-3 (PDE3), could be a viable strategy to shed light on the polypharmacological profile of coumarin-based compounds. Docking simulations towards PDE3 were also carried out.

Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives / Kontogiorgis, Christos; Nicolotti, Orazio; Mangiatordi, Giuseppe Felice; Tognolini, Massimiliano; Karalaki, Foteini; Giorgio, Carmine; Patsilinakos, Alexandros; Carotti, Angelo; Hadjipavlou Litina, Dimitra; Barocelli, Elisabetta. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - (2015), pp. 1-9-9. [10.3109/14756366.2014.995180]

Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives

TOGNOLINI, Massimiliano;GIORGIO, Carmine;BAROCELLI, Elisabetta
2015-01-01

Abstract

The interest towards coumarin-based structures stems from their polypharmacological profile. Herein, we present a series of Mannich bases and 7-azomethine-linked coumarin derivatives exhibiting antiplatelet and antithrombotic activities, in addition to the already known anti-inflammatory and antioxidant activities. Among others, compounds 15 and 16 were found to be the most potent and selective inhibitors of platelet aggregation whereas compound 3 also proved to be the most potent in the clot retraction assay. Structure-activity relationship studies were conducted to elucidate the molecular determinants responsible for the herein observed activities. The chance of inhibiting cyclooxygenase-1 was also investigated for evaluating the platelet aggregation induced by arachidonic acid. Taken together, these results suggest that the investigation of other targets connected to the antiplatelet activity, such as phosphodiesterase-3 (PDE3), could be a viable strategy to shed light on the polypharmacological profile of coumarin-based compounds. Docking simulations towards PDE3 were also carried out.
2015
Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives / Kontogiorgis, Christos; Nicolotti, Orazio; Mangiatordi, Giuseppe Felice; Tognolini, Massimiliano; Karalaki, Foteini; Giorgio, Carmine; Patsilinakos, Alexandros; Carotti, Angelo; Hadjipavlou Litina, Dimitra; Barocelli, Elisabetta. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - (2015), pp. 1-9-9. [10.3109/14756366.2014.995180]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2788295
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