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Antithrombotic Activity of a Newly Synthesized Coumarin Derivative 3‐(5‐Hydroxy‐2,2‐dimethyl‐chroman‐6‐yl)‐N‐{2‐[3‐(5‐hydroxy‐2,2‐dimethyl‐chroman‐6‐yl)‐propionylamino]‐ethyl}‐propionamide
Author(s) -
Jain Manish,
Surin William R.,
Misra Ankita,
Prakash Prem,
Singh Vishal,
Khanna Vivek,
Kumar Satish,
Siddiqui Hefazat H.,
Raj Kanwal,
Barthwal Manoj K.,
Dikshit Madhu
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12000
Subject(s) - antithrombotic , pharmacology , platelet , thrombus , medicine , thrombosis , chemistry , platelet activation , bleeding time , platelet aggregation
Anti‐platelet therapy is a useful strategy to prevent acute thromboembolic artery occlusions. This study was designed to assess the efficacy of seselin derivatives against murine pulmonary thromboembolism, bleeding time, platelet activation and thrombosis. Administration of C3 (16 mg/kg) offered 70% protection against collagen‐ and epinephrine‐induced pulmonary thromboembolism and 30% protection against arachidonic acid‐induced death in mice, without adversely affecting bleeding time. No significant difference was observed by C3 in ferric chloride‐induced arterial thrombosis in rats. Significant reduction in thrombus weight was observed in arteriovenous shunt model. In rat PRP, C3 reduced ADP and collagen‐induced platelet aggregation. In chronic hamster model of dyslipidemia, administration of C3 (16 mg/kg p.o. for 90 days) had no effect on plasma lipids, vasoreactivity and platelet adhesion. C3 fed hamsters showed reduced whole‐blood aggregation response to ADP and collagen compared to HC‐fed hamsters. In addition, C3 augmented thrombin time; however, time to occlusion was not increased. These results convincingly demonstrated that C3 is a novel molecule that reduces the risk of thrombosis and alleviates prothrombotic state associated with hyperlipidemia without any adverse effect on bleeding time. The high benefit/risk ratio of this compound makes it a suitable candidate for future valid studies.