186255-65-2Relevant articles and documents
Synthesis, characterization, and anticoagulant activity of new functionalized biscoumarins
Mustafa, Yasser Fakri,Mohammed, Eman Tareq,Khalil, Raghad Riyadh
, p. 4461 - 4468 (2021/08/07)
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.
Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents
Ji, Qinggang,Ge, Zhiqiang,Ge, Zhixing,Chen, Kaizhi,Wu, Hualong,Liu, Xiaofei,Huang, Yanrong,Yuan, Lvjiang,Yang, Xiaolan,Liao, Fei
, p. 166 - 176 (2015/12/04)
A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the Km of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-Nacetylglucosamine, and the result of the Ki showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 μg/mL to 2 μg/Ml while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational.
