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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

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

Eur J Med Chem. 2015 Jul 15;100:119-28.

PMID: 26079088

Abstract:

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-triazolyl 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS7931310	2-(4-Methylpiperazin-1-yl)pyrimidin-5-ylboronic acid			Price

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