Synthesis, in vivo Anticoagulant Evaluation and Molecular Docking Studies of Bicoumarins Obtained from Furocoumarin Peucedanin

Synthesis, in vivo Anticoagulant Evaluation and Molecular Docking Studies of Bicoumarins Obtained from Furocoumarin Peucedanin Full article

Journal

Medicinal Chemistry
ISSN: 1573-4064 , E-ISSN: 1875-6638

Output data

Year: 2016, Volume: 12, Number: 7, Pages: 674-683 Pages count : 10 DOI: 10.2174/1573406412666160129105115

Tags

Bicoumarins; peucedanin; click reactions; anticoagulant; molecular docking

Authors

Lipeeva Alla V. ¹ , Khvostov Mikhail V. ² , Baev Dmitry S. ² , Shakirov Makhmut M. ³ , Tolstikova Tatijana G. ² , Shults Elvira E. ^1,4

Affiliations

1	(Данные Web of science) Novosibirsk Organ Chem Inst, Lab Med Chem, Siberian Branch, Novosibirsk, Russia
2	(Данные Web of science) Russian Acad Sci, Novosibirsk Organ Chem Inst, Lab Pharmacol Res, Siberian Branch, Novosibirsk, Russia
3	(Данные Web of science) Russian Acad Sci, Novosibirsk Organ Chem Inst, Lab Phys Methods, Siberian Branch, Novosibirsk, Russia
4	(Данные Web of science) Novosibirsk State Univ, Novosibirsk, Russia

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.

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 OpenAlex

Published print:

Sep 27, 2016

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

DB	Citing
Web of science	16
Scopus	16
Elibrary	17
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