Synthesis and antibacterial activity of flavonols

Abstract

Flavonol, also known as 3-hydroxylflavonone, is a kind of natural flavonoid compounds that have various important physiological and pharmacological activities. This study aimed to establish the structure-activity relationship of flavonols against antibacterial activity, in order to provide the basis for further drug design. In all, 20 flavonols were synthesized, and their antibacterial activities were identified. Twenty flavonols, including 1 new compound, were synthesized by using the one-pot method or three-step approach, based on the Algar-Flynn-Oyamada (AFO) reaction. Their anti-microbial activities against Bacillus subtilis, Saccharomycetes, and Aspergillus Niger were subsequently evaluated using the Oxford cup method by using dimethyl sulfoxide as a negative control and methicillin as a positive control. Our results indicated that these flavonols possess satisfactory antibacterial activity to Bacillus subtilis, but have no obvious inhibitive effect against Saccharomycetes and Aspergillus Niger. Structure-activity relationship indicated that halo-substitution at either A- or B-ring (compounds 7, 8, 17, 19, and 20) might strengthen the antibacterial activity. In addition, 5-methoxy-substituted flavonols (compounds 12, 13, and 14) exhibited improved antibacterial activities relative to the ones with non-substitution at the 5-position (12 vs. 2, 13 vs. 3, 14 vs. 1). Our results provide preliminary data for designing and discovering new leading compounds with antibacterial activities.