New Derivatives of 1-(3-Methyl-1-Benzofuran-2-yl)Ethan-1-one: Synthesis and Preliminary Studies of Biological Activity

Abstract

A set of nine derivatives, including five brominated compounds, was synthesized and the structures of these novel compounds were confirmed using 1H and 13C NMR as well as ESI MS spectra. These compounds were tested on four different cancer cell lines, chronic myelogenous leukemia (K562), prostate cancer (PC3), colon cancer (SW620), human kidney cancer (Caki 1), and on healthy human keratocytes (HaCaT). MTT results reveal that two newly developed derivatives (6 and 8) exhibit selective action towards K562 cells and no toxic effect in HaCat cells. The biological activity of these two most promising compounds was evaluated by trypan blue assay, reactive oxygen species generation, and IL-6 secretion. To investigate the proapoptotic activity of selected compounds, the two following types of tests were performed: Annexin V Apoptosis Detection Kit I and Caspase-Glo 3/7 assay. The studies of the mechanism showed that both compounds have pro-oxidative effects and increase reactive oxygen species in cancer cells, especially at 12 h incubation. Through the Caspase-Glo 3/7 assay, the proapoptotic properties of both compounds were confirmed. The Annexin V-FITC test revealed that compounds 6 and 8 induce apoptosis in K562 cells. Both compounds inhibit the release of proinflammatory interleukin 6 (IL-6) in K562 cells. Additionally, all compounds were screened for their antibacterial activities using standard and clinical strains. Within the studied group, compound 7 showed moderate activity towards Gram-positive strains in antimicrobial studies, with MIC values ranging from 16 to 64 µg/mL.

Special Issue “Development and Synthesis of Biologically Active Compounds”

“…Napiórkowska et al [22][23][24] devoted several years to the study of the biological properties of benzofuran derivatives, resulting in the identification of bromosubstituted benzofurans possessing high antitumor activity. Among the series of novel 2-acetyl-3-(bromo)methyl benzofurans, two bromomethyl derivatives exhibited selective cytotoxic effect to leukemia cancer cells (K562) compared to that against normal cells (HaCaT) with a favorable therapeutic index.…”