Synthesis 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 synt...
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MDPI AG
2022-09-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/9/280 |
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| author | Xing Wang Hao-Yu Fu Wei He Yu-Ting Xiang Ze-Cheng Yang Yi Kuang Sheng-Xiang Yang |
| author_facet | Xing Wang Hao-Yu Fu Wei He Yu-Ting Xiang Ze-Cheng Yang Yi Kuang Sheng-Xiang Yang |
| author_sort | Xing Wang |
| collection | DOAJ |
| description | 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. |
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| spelling | doaj.art-cfad75197a6d4dd9a9c5b8514644135d2023-11-23T15:39:15ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-09-014494087409910.3390/cimb44090280Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant BacteriaXing Wang0Hao-Yu Fu1Wei He2Yu-Ting Xiang3Ze-Cheng Yang4Yi Kuang5Sheng-Xiang Yang6Zhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang A&F University, Hangzhou 311300, ChinaZhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang A&F University, Hangzhou 311300, ChinaZhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang A&F University, Hangzhou 311300, ChinaZhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang A&F University, Hangzhou 311300, ChinaZhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang A&F University, Hangzhou 311300, ChinaZhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang A&F University, Hangzhou 311300, ChinaZhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, College of Chemistry and Materials Engineering, Zhejiang A&F University, Hangzhou 311300, ChinaThe 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.https://www.mdpi.com/1467-3045/44/9/280biphenylsaucuparinphytoalexinsantibacterial activityantibiotic-resistant bacteria |
| spellingShingle | Xing Wang Hao-Yu Fu Wei He Yu-Ting Xiang Ze-Cheng Yang Yi Kuang Sheng-Xiang Yang Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria Current Issues in Molecular Biology biphenyls aucuparin phytoalexins antibacterial activity antibiotic-resistant bacteria |
| title | Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria |
| title_full | Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria |
| title_fullStr | Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria |
| title_full_unstemmed | Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria |
| title_short | Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria |
| title_sort | synthesis and antibacterial activity evaluation of biphenyl and dibenzofuran derivatives as potential antimicrobial agents against antibiotic resistant bacteria |
| topic | biphenyls aucuparin phytoalexins antibacterial activity antibiotic-resistant bacteria |
| url | https://www.mdpi.com/1467-3045/44/9/280 |
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