biostudies-literatureWang Xthe Key Research &amp; Development Projects of Zhejiang Provincethe Zhejiang A&amp;F University Scientific Research and Development Fund Projectthe Fundamental Research Funds for the Provincial Universities of Zhejiangthe Public Welfare Technology and Application Research Project supported by Sci-ence Technology Department of Zhejiang ProvinceNational Natural Science Foundation of Chinathe "Pioneer" and "Leading Goose" R&amp;D Program of Zhejiangthe Ability Establishment of Sustainable Use for Valuable Chinese Medicine resourcesNational College Students Innovation and Entrepreneurship Training Program4087-4099https://www.ebi.ac.uk/biostudies/studies/S-EPMC9497828biostudies-literatureUnknown44(9)The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, a series of biphenyl and dibenzofuran derivatives were designed and synthesized by Suzuki-coupling and demethylation reactions in moderate to excellent yields (51-94% yield). Eleven compounds exhibited potent antibacterial activities against the prevalent antibiotic-resistant Gram-positive and Gram-negative pathogens, among which compounds 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (<b>6i</b>) and 5-(9<i>H</i>-carbazol-2-yl) benzene-1,2,3-triol (<b>6m</b>) showed the most potent inhibitory activities against methicillin-resistant <i>Staphylococcus aureus</i> and multidrug-resistant <i>Enterococcus faecalis</i> with MIC (minimum inhibitory concentration) values as low as 3.13 and 6.25 μg/mL, respectively. Compounds 3',5'-dimethyl-[1,1'-biphenyl]-3,4,4',5-tetraol (<b>6e</b>), 4'-fluoro-[1,1'-biphenyl]-3,4,5-triol (<b>6g</b>), and 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (<b>6i</b>) showed comparable inhibitory activities with ciprofloxacin to Gram-negative bacterium carbapenems-resistant <i>Acinetobacter baumannii</i>. Study of the structure-activity relationship indicated that a strong electron-withdrawing group on the A ring and hydroxyl groups on the B ring of biphenyls were beneficial to their antibacterial activities, and for benzo-heterocycles, <i>N</i>-heterocycle exhibited optimal antibacterial activity. These results can provide novel structures of antibacterial drugs chemically different from currently known antibiotics and broaden prospects for the development of effective antibiotics against antibiotic-resistant bacteria.Current issues in molecular biologySynthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria.PMC94978282017FR03620603022022C02023321012282020C030902021TD001GN21B020001202110341018, 202010341055Fu HYHe WYang ZCYang SXWang XXiang YTKuang YfalseSynthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria.The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, a series of biphenyl and dibenzofuran derivatives were designed and synthesized by Suzuki-coupling and demethylation reactions in moderate to excellent yields (51-94% yield). Eleven compounds exhibited potent antibacterial activities against the prevalent antibiotic-resistant Gram-positive and Gram-negative pathogens, among which compounds 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (<b>6i</b>) and 5-(9<i>H</i>-carbazol-2-yl) benzene-1,2,3-triol (<b>6m</b>) showed the most potent inhibitory activities against methicillin-resistant <i>Staphylococcus aureus</i> and multidrug-resistant <i>Enterococcus faecalis</i> with MIC (minimum inhibitory concentration) values as low as 3.13 and 6.25 μg/mL, respectively. Compounds 3',5'-dimethyl-[1,1'-biphenyl]-3,4,4',5-tetraol (<b>6e</b>), 4'-fluoro-[1,1'-biphenyl]-3,4,5-triol (<b>6g</b>), and 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (<b>6i</b>) showed comparable inhibitory activities with ciprofloxacin to Gram-negative bacterium carbapenems-resistant <i>Acinetobacter baumannii</i>. Study of the structure-activity relationship indicated that a strong electron-withdrawing group on the A ring and hydroxyl groups on the B ring of biphenyls were beneficial to their antibacterial activities, and for benzo-heterocycles, <i>N</i>-heterocycle exhibited optimal antibacterial activity. These results can provide novel structures of antibacterial drugs chemically different from currently known antibiotics and broaden prospects for the development of effective antibiotics against antibiotic-resistant bacteria.2022-01-01T00:00:00Z2022 Sep2025-04-21T14:38:06.961Z2025-04-21T14:38:06.961ZS-EPMC94978283613519210.3390/cimb44090280