Some Experimental Studies on the Anticoagulant Activity of the Synthetic Coumarin Derivatives

Abstract

Intensive research efforts have been devoted to the design and synthesis of 4-hydroxycoumarin derivatives as anticoagulants. The main purpose of this study was to report the synthesis of some coumarin-type derivatives, including, 4-aryl-1,2-dihydro-6-(4-hydroxy-2-oxo-2H-chromene-3-yl)-2-oxopyridin-3-carbonitrile (3, 4). The structure of the synthesized compounds has been verified on the basis of literature data and spectroscopic measurements such as NMR, MS and IR. In addition, there were two objectives for the study: first, to test these synthetic derivatives in vivo for their anticoagulant effects in the laboratory male mice (Mus musculus swiss albino). Second, to compare between the in vivo activity of these synthetic derivatives and that of Warfarin (CAS 81-81-2), which is the most commonly used anticoagulant. Prothrombin time (PT) was used as the value to compare the anticoagulant properties of the synthesized compounds (1, 3, 4) and warfarin. The time for plasma to solidify following the addition of warmed thrombokinase suspension was taken as the PT. Results of this study revealed that the most potent compound of the synthesized derivatives was 4-(3-bromo-phenyl)-6-(4-hydroxy-2-oxo-2Hchromene-3-yl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (4), which shows higher anticoagulant activity (PT(s) 21.30) than warfarin (PT(s) 14.60). However, Anticoagulant activity was also associated with toxicity by the all synthesized compounds. Conclusion and practical importance: Synthesized coumarins (3 and 4) increased PT when compared to saline treated control group and other coumarins. They are potentially antithrombotic drug candidates for further elaboration. Compounds 3 and 4 need to be further tested for the side effects so that they can be introduced into clinical trials.