Synthesis, characterization, and anticoagulant activity of new functionalized biscoumarins

Abstract

Despite their rarity and structural complexity, natural and synthetic biscoumarins have polarized much attention from investigators particularly due to their characteristic activity as anticoagulant agents. In this work, a panel of twelve functionalized biscoumarins was synthesized in two schematic steps; the first one started by condensing various phenol-based derivatives with malonic acid via a Pechmann-type reaction yielding alkyl-substituted 4-hydroxycoumarins herein symbolized as (E1-E12). The latter compounds were undergone a self-coupling under the influence of methylene iodide to afford the target functionalized biscoumarins, which were symbolized as (EY1-EY12). The potential of the synthesized biscoumarins as anticoagulant applicants was investigated in vivo using rabbit as an animal model. The employed assay was the prothrombin time that was monitored after three and five days of the last oral treatment. The results gathered from this test revealed that the synthesized biscoumarins have a promising anticoagulant activity compared with warfarin as a standard anticoagulant drug, with privileged influence contributed to those substituted at position 7 of the coumarin framework. The authors concluded that the substitution of an alkyl group at that position of the coumarin monomer may intensify the anticoagulant activity of the prepared biscoumarins. Also, this intensity was directly proportionated to the increase in the molecular weight of this alkyl group. Accordingly, the synthesized biscoumarins possessing this property would provide an efficient base for synthesizing new compounds, which have a promising anticoagulant effect.

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“…Antioxidants are mainly found in vegetarian foods. Phyto-chemicals such as terpenoids, coumarin, alkaloids, flavonoids, and phenols, specifically, are essential antioxidant compounds with a variety of nutritional advantages [46,47]. These phytochemicals are classified as secondary metabolites as they are found in smaller quantities in vegetation than primary metabolites and are found in specialized plant parts [48][49].…”

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“…To identify a variety of phytochemical compounds, successful methods of analysis have been used to conduct phytochemical screening of Citrullus L. seed aqueous extracts [11][12][13][14]. The inspected phytochemical compounds were classified into two groups: essential and nonessential fruit-derived chemicals.…”

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“…Coumarins may be found in a wide range of natural sources and can also be prepared through a range of chemical interactions [26]. The majority of natural and synthetic coumarin-based compounds studied have demonstrated encouraging biomedical potential, such as antimicrobial [27], antiparasitic [28], antiinflammatory [29], antioxidant [30], antithrombotic [31], anti-Alzheimer [32],…”