Synthesis of 1H-1,2,3-triazole linked aryl(arylamidomethyl) - dihydrofurocoumarin hybrids and analysis of their cytotoxicity

Synthesis of 1H-1,2,3-triazole linked aryl(arylamidomethyl) - dihydrofurocoumarin hybrids and analysis of their cytotoxicity Full article

Journal

European Journal of Medicinal Chemistry
ISSN: 0223-5234 , E-ISSN: 1768-3254

Output data

Year: 2015, Volume: 100, Pages: 119-128 Pages count : DOI: 10.1016/j.ejmech.2015.05.016

Tags

Azides; Alkynes; 1,2,3-Triazoles; Click chemistry; Cytotoxicity

Authors

Lipeeva Alla V. ¹ , Pokrovsky Mikhail A. ² , Baev Dmitry S. ¹ , Shakirov Makhmut M. ¹ , Bagryanskaya Irina Y. ^1,2 , Tolstikova Tatijana G. ^1,2 , Pokrovsky Andrey G. ² , Shults Elvira E. ^1,2

Affiliations

1	(Данные Web of science) Russian Acad Sci, Novosibirsk Organ Chem Inst, Siberian Branch, Med Chem Lab, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Dept Med, Novosibirsk 630090, Russia

A series of 2-(4-R-triazolyl)substituted 3-oxo-2,3-dihydrofurocoumarins have been synthesized by a regioselective cycloaddition of 2-azidooreoselone 1 or 2-azido-9-[(4-methylpiperazin-1-yl)methyl] oreoselone 2 with various alkynes in the presence of Cu(II)/ascorbate in water/methylene chloride reaction medium. The structure of 2-azidooreoselone was established by X-ray structure analysis. The cytotoxicity of 2-substituted dihydrofurocoumarins was determined against three cancer cell lines (CEM-13, MT-4, U-937) using the conventional MTT assays. Among the tested molecules, most of the analogs displayed better cytotoxic activity then the parent natural furocoumarin peucedanin 3. The activity and selectivity to the cell line increased even further in the series of 2-(4-(2,3-dihydrobenzo[b][1,4]dioxine) triazolyl)-3-oxo-2,3-dihydrofurocoumarins and 2-(4-aryltriazolyl)-3-oxo-2,3-dihydrofurocoumarins having the (4-methylpiperazin-1-ylmethyl) substituent in the 9-th position. The most active compound 20 contain the 4-hydroxy-3-methoxybenzamidomethyl substituent in the 4-th position at the triazole ring of 2-(triazol-1-yl)dihydrofurocoumarins. The obtained 2-triazoly1 substituted dihydrofurocoumarins were studied as inhibitors of phosphodiesterase (PDE-4B) using docking experiments. As a result of virtual screening 3 compounds are selected based on minimum binding energy. The interactions of the most active compound and amino acid residues in the binding site were studied. (C) 2015 Elsevier Masson SAS. All rights reserved.

Lipeeva A.V. , Pokrovsky M.A. , Baev D.S. , Shakirov M.M. , Bagryanskaya I.Y. , Tolstikova T.G. , Pokrovsky A.G. , Shults E.E.
Synthesis of 1H-1,2,3-triazole linked aryl(arylamidomethyl) - dihydrofurocoumarin hybrids and analysis of their cytotoxicity
European Journal of Medicinal Chemistry. 2015. V.100. P.119-128. DOI: 10.1016/j.ejmech.2015.05.016 WOS Scopus

Published print:

Jul 1, 2015

Web of science	WOS:000358097200013
Scopus	2-s2.0-84931260603
OpenAlex	W247059929