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Synthesis of 1,2,3-triazole-substituted coumarins and also 1,2,3-triazolyl or 1,2,3-triazolylalk-1-inyl-linked coumarin-2,3-furocoumarin hybrids was performed by employing the cross-coupling and copper catalyzed azide-alkyne cycloaddition reaction approaches. The synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus , Bacillius subtilis , Actinomyces viscosus and Escherichia coli bacterial strains. Coumarin-benzoic acid hybrids 4с , 42с and 3-((4-acetylamino-3-(methoxycarbonyl)phenyl)ethynyl)coumarin ( 29 ) showed promising activity against S . aureus strains, and the 1,2,3-triazolyloct-1-inyl linked coumarin-2,3-furocoumarin hybrid 37c was endowed with high selectivity against B. subtilis and E. coli species. The in vitro antibacterial activity of 4с , 29 , 37c and 42с can potentially be compared with that of a number of modern antibiotic drugs used in the clinic, suggesting promising prospects for further research. A detailed study of the molecular interactions with the targeted protein MurB was performed using docking simulations and the obtained results are quite promising.

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., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)