title: 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.
abstract: 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.
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226001, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Jain
authors.forename: William R
authors.initials: WR
authors.lastname: Surin
authors.forename: Ankita
authors.initials: A
authors.lastname: Misra
authors.forename: Prem
authors.initials: P
authors.lastname: Prakash
authors.forename: Vishal
authors.initials: V
authors.lastname: Singh
authors.forename: Vivek
authors.initials: V
authors.lastname: Khanna
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.forename: Hefazat H
authors.initials: HH
authors.lastname: Siddiqui
authors.forename: Kanwal
authors.initials: K
authors.lastname: Raj
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Barthwal
authors.forename: Madhu
authors.initials: M
authors.lastname: Dikshit
mesh_terms: D000818:Animals; D001760:Bleeding Time; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006224:Cricetinae; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000188:drug therapy; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy
chemical_list: C583450:3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-N-(2-(3-(5-hydroxy-2,2-dimethyl-chroman-6-yl)-propionylamino)-ethyl)-propionamide; D002839:Chromans; D003374:Coumarins; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; C516746:seselin