Synthesis, physicochemical characterization and biological activity of novel pyrrole flavones

Cancer remains one of the most significant health issues worldwide. By designing compounds with anticancer activity characterized by high selectivity towards cancer cells, medicinal chemistry focuses on the protection of healthy cells and tissues. In this study, we present the hybrid pharmacophore approach, which afforded a series of new pyrrole flavones. The synthetic strategy was based on the Paal-Knorr pyrrole synthesis, starting from aminoflavones through their condensation with 1,4-diketones and leading to 6- and 7-(pyrrol-1-yl) flavones. The isolated products underwent characterization using NMR and UV-VIS spectroscopy, mass spectrometry, TGA, DSC, and Microtox analyses. For all pyrrole flavones, single crystals were obtained and subjected to X-ray diffraction experiments. Their cytotoxic activity was assessed on two human bladder cancer cell lines (5637 and HT-1376) and one non-cancerous (MRC-5) cell line, showing the potential as anticancer agents. Flavone derivative with the 6-(2-methyl-5-phenylpyrrol-1-yl) moiety was active in the MTT assay towards 5637 and HT-1376 cancer cells after 24 h of incubation with IC₅₀ values of 2.97 µM and 5.89 µM, respectively. Notably, flavone derivative with 7-(2-methyl-5-phenylpyrrol-1-yl) revealed cytotoxic activity towards 5637 and HT-1376 cells with IC₅₀ values of 7.39 µM and 13.54 µM, respectively, without any effect on the viability of MRC-5 cells.