Novel functionalized phenyl acetate derivatives of benzo [e]-bispyrone fused hybrids: Synthesis and biological activities

Abstract

Eighteen novel functionalized phenyl acetate derivatives of benzo[e]-bispyrone fused hybrids and their three precursors are developed in this study. The precursor acetic acid congeners of benzo[e]-bispyrone fused hybrids (Y1, Y8, and Y15) were created by combining acetone dicarboxylic acid and three resorcinol-based compounds. They were utilized in the preparation of novel functionalized phenyl acetate derivatives of benzo[e]-bispyrone fused hybrids (Y2-Y7, Y9-Y14, and Y16-Y21). Six in vitro biological activities were investigated for the synthesized precursors and their functionalized phenyl acetate derivatives. First, the reactive species-caging activity was tested against DPPH and hydroxyl radicals. Second, the cellular viability-terminating activity was assayed using MTT-visual probing methodology against six common cancerous cell lines. Third, fourth, and fifth activities, collectively termed microbial-shedding potential, were examined using a microdilution broth methodology against six aerobic pathogenic bacterial strains, four anaerobic pathogenic bacterial strains, and two pathogenic fungal strains, respectively. Finally, the blood sugar-dropping activity was assessed against two related enzymes. Moreover, the toxic effects of the twenty-one synthesized compounds were assessed against one normal human cell line and one non-pathogenic bacterial strain. The results showed that the fused hybrids' methoxyphenyl acetate derivatives (Y2, Y9, and Y16) had the greatest reactive species-caging, anaerobic pathogenic bacterial-shooting, and blood sugar-dropping activities. In terms of cellular viability-terminating activity, the fluorophenyl acetate derivatives (Y4, Y11, and Y18) demonstrated the greatest activity against the tested cancerous cell lines while causing the least toxicity to the normal cell line. Chlorophenyl acetate derivatives had the highest aerobic pathogen-shedding activity while causing the least toxicity on normal bacterial strains (Y5, Y12, and Y19). Finally, the precursors and derivatives with flourophenyl or chlorophenyl acetate demonstrated the highest levels of fungal-shooting activity, exceeding the reference. The researchers concluded from these observations that the synthesized precursors and their derivatives provided several biosafe scaffolds with multiple and selective activities.