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.

Inhibition of PAI-1 Activity by Toddalolactone as a Mechanism for Promoting Blood Circulation and Removing Stasis by Chinese Herb Zanthoxylum nitidum var. tomentosum

“…Dabigatran, which is considered to be a new derivative of warfarin, might become an alternative drug in the treatment of venous thromboembolism (Bansal and Ren, 2016). A kind of coumarin derivative has been demonstrated to prevent collagen- and epinephrine-induced pulmonary thromboembolism and significantly reduce thrombus weight in arteriovenous shunt model (Jain et al, 2013). However, the exact molecular mechanisms of these antithrombotic drugs are unclear.…”

Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells

“…Coumarins are a family of compounds widely distributed in plants, bacteria, and fungi; they present various pharmacological properties, including antibacterial [21], antimutagenic [22], anti-inflammatory [23], anticoagulant [24–26], antithrombotic [27, 28], and anticancer activities [29]. In cancers, coumarins target a number of pathways or signaling molecules, including cell cycle progression, angiogenesis, heat shock protein 90, telomerase, mitosis, carbonic anhydrase, monocarboxylate transporters, aromatase, and sulfatase [30].…”

Gastroprotective Efficacy and Safety Evaluation of Scoparone Derivatives on Experimentally Induced Gastric Lesions in Rodents

“…Coumarin compounds, a large class of lactones, are medicinal agents that have attracted interest due to their potential for preventing and treating diseases having a wide range of biological activities; amazingly, these compounds have shown anti-coagulant [ 6 , 7 , 8 ], anti-neurodegenerative [ 9 , 10 , 11 ], anti-oxidant [ 12 , 13 , 14 , 15 ], anti-cancer [ 15 , 16 , 17 , 18 , 19 , 20 ], anti-microbial [ 21 , 22 , 23 ], anti-parasitic [ 24 , 25 , 26 ], and anti-inflammatory [ 27 , 28 , 29 , 30 ] efficacies. Recent studies have also demonstrated that coumarin compounds possess gastrointestinal protective properties [ 31 , 32 , 33 , 34 ].…”