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High biological activity of natural furocoumarins is often linked to a series of adverse side effects, e.g., genotoxicity. This makes it desirable to develop semi-synthetic derivatives with reduced negative activity while retaining or even enhancing the positive properties. Previously, we have studied the genotoxic activity of a library of twenty-one 1,2,3-triazolyl-modified furocoumarins and 2,3-dihydrofurocoumarins and identified modifications that minimize the negative properties. In the current article, we report on an investigation into the cytotoxic activity of the same library. We have aimed to rank the substances in order of the severity of their cytotoxicity and therefore to predict, with the use of statistical processing, the most promising substituents for the furocoumarin scaffold., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Fluorescent labeling is a widely-used approach in the study of intracellular processes. This method is becoming increasingly popular for studying small bioactive molecules of natural origin; it allows us to estimate the vital intracellular changes which occur under their influence. We propose a new approach for visualization of the intracellular distribution of triterpene acids, based on fluorescent labeling by fluoresceine isothiocyanate. As a model compound we took the most widely-used and best-studied acid in the ursane series - ursolic acid, as this enabled us to compare the results obtained during our research with the available data, in order to evaluate the validity of the proposed method. Experimental tracing of the dynamics of penetration and distribution of the labeled ursolic acid has shown that when the acid enters the cell, it initially localizes on the inner membranes where the predicted target Akt1/protein kinase B - a protein that inhibits apoptosis - is located., (Copyright © 2018. Published by Elsevier Inc.)

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.)