Abstract: Background: Synthesis of 7,7'-linked bicoumarins, 3,3'-linked bi(2-isopropyl) psoralens as well as 1H-1,2,3-triazole linked coumarin-2,3-dihydrofurocoumarin and furocoumarin-2,3-dihydrofurocoumarin hybrids was performed by two alternative pathways, either involving a catalyzed transformations of the ethynyl derivatives of plant coumarins-peucedanin or peuruthenicin. Objective and Methods: The Sonogashira reaction of 7-ethynyl coumarins or 3-ethynyl-2-isopropylpsoralen with the subsequent coumarin triflates led to 7,7'-linked bicoumarins or 3,3'-linked bipsoralens. 1,2,3-Triazole linked coumarin-2,3-dihydrofurocoumarin or furocoumarin-2,3-dihydrofurocoumarin hybrids were synthesized by a regioselective Cu-catalyzed cycloaddition reaction of 2-azidooreoselone with 7-alkynylcoumarins or 3-ethynyl-2-isopropylpsoralen. Results: Pharmacological screening of synthesized bicoumarins for anticoagulant activity in vivo revealed that coumarin-dihydrofurocoumarin hybrids linked with a 1,2,3-triazole ring 20 and 22 were the most active compounds. The presented prothrombin time (PT) values comparable to the reference drug warfarin in a dose 100 mg/kg. Docking studies were undertaken to gain insight into the possible binding mode of these compounds with the coagulation factor Xa (FXa) binding site. Conclusion: The moderate toxicity of compounds 20 and 22 (LD50 valuewas more than 3000 mg/kg) encouraged the further design of therapeutically relevant analogues based on these novel type of coumarin hybrids.

Cite: Lipeeva A.V. , Khvostov M.V. , Baev D.S. , Shakirov M.M. , Tolstikova T.G. , Shults E.E.
Synthesis, in vivo Anticoagulant Evaluation and Molecular Docking Studies of Bicoumarins Obtained from Furocoumarin Peucedanin
Medicinal Chemistry. 2016. V.12. N7. P.674-683. DOI: 10.2174/1573406412666160129105115 WOS Scopus РИНЦ

Dates:

Published print:

Sep 27, 2016

Identifiers:

Web of science	WOS:000385569600009
Scopus	2-s2.0-84991108789
Elibrary	27577195
OpenAlex	W2253980805

Altmetrics: