Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism
Due to the emergence and wide spread of methicillin-resistant Staphylococcus aureus, the treatment of this kind of infection becomes more and more difficult. To solve the problem of drug resistance, it is urgent to develop new antibiotics to avoid the most serious situation of no drug available. Thr...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.1035741/full |
| _version_ | 1811194710753017856 |
|---|---|
| author | Li Jiang Yuanyuan Ma Yanshi Xiong Yanhui Tan Xuemin Duan Xiangwen Liao Jintao Wang |
| author_facet | Li Jiang Yuanyuan Ma Yanshi Xiong Yanhui Tan Xuemin Duan Xiangwen Liao Jintao Wang |
| author_sort | Li Jiang |
| collection | DOAJ |
| description | Due to the emergence and wide spread of methicillin-resistant Staphylococcus aureus, the treatment of this kind of infection becomes more and more difficult. To solve the problem of drug resistance, it is urgent to develop new antibiotics to avoid the most serious situation of no drug available. Three new Ru complexes [Ru (dmob)2PMA] (PF6)2 (Ru-1) [Ru (bpy)2PMA] (PF6)2 (Ru-2) and [Ru (dmb)2PMA] (PF6)2 (Ru-3) (dmob = 4,4′-dimethoxy-2,2′-bipyridine, bpy = 2,2′-bipyridine, dmb = 4,4′-dimethyl-2,2′-bipyridine and PMA = N-(4-(1H-imidazo [4,5-f] [1,10] phenanthrolin-2-yl) -4-methyl-N-(p-tolyl) aniline) were synthesized and characterized by 1H NMR, 13C NMR and HRMS. The detailed molecular structure of Ru-3 was determined by single crystal X-ray diffraction. Their antibacterial activities against Staphylococcus aureus (Staphylococcus aureus) were obvious and Ru-3 showed the best antibacterial effect with the minimum inhibitory concentration value of 4 μg ml−1. Therefore, further study on its biological activity showed that Ru-3 can effectively inhibit the formation of biofilm and destroy cell membrane. In vitro hemolysis test showed that Ru-3 has almost negligible cytotoxicity to mammalian red blood cells. In the toxicity test of wax moth insect model, Ru-3 exhibited low toxicity in vivo. These results, combined with histopathological studies, strongly suggest that Ru-3 was almost non-toxic. In addition, the synergistic effect of Ru-3 with common antibiotics such as ampicillin, chloramphenicol, tetracycline, kanamycin and gentamicin on Staphylococcus aureus was detected by chessboard method. Finally, in vivo results revealed that Ru-3 could obviously promote the wound healing of Staphylococcus aureus infected mice. |
| first_indexed | 2024-04-12T00:31:15Z |
| format | Article |
| id | doaj.art-b8b31163089f4c31b02d3473949cd342 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-12T00:31:15Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-b8b31163089f4c31b02d3473949cd3422022-12-22T03:55:20ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-10-011010.3389/fchem.2022.10357411035741Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanismLi Jiang0Yuanyuan Ma1Yanshi Xiong2Yanhui Tan3Xuemin Duan4Xiangwen Liao5Jintao Wang6Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, ChinaState Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, ChinaDue to the emergence and wide spread of methicillin-resistant Staphylococcus aureus, the treatment of this kind of infection becomes more and more difficult. To solve the problem of drug resistance, it is urgent to develop new antibiotics to avoid the most serious situation of no drug available. Three new Ru complexes [Ru (dmob)2PMA] (PF6)2 (Ru-1) [Ru (bpy)2PMA] (PF6)2 (Ru-2) and [Ru (dmb)2PMA] (PF6)2 (Ru-3) (dmob = 4,4′-dimethoxy-2,2′-bipyridine, bpy = 2,2′-bipyridine, dmb = 4,4′-dimethyl-2,2′-bipyridine and PMA = N-(4-(1H-imidazo [4,5-f] [1,10] phenanthrolin-2-yl) -4-methyl-N-(p-tolyl) aniline) were synthesized and characterized by 1H NMR, 13C NMR and HRMS. The detailed molecular structure of Ru-3 was determined by single crystal X-ray diffraction. Their antibacterial activities against Staphylococcus aureus (Staphylococcus aureus) were obvious and Ru-3 showed the best antibacterial effect with the minimum inhibitory concentration value of 4 μg ml−1. Therefore, further study on its biological activity showed that Ru-3 can effectively inhibit the formation of biofilm and destroy cell membrane. In vitro hemolysis test showed that Ru-3 has almost negligible cytotoxicity to mammalian red blood cells. In the toxicity test of wax moth insect model, Ru-3 exhibited low toxicity in vivo. These results, combined with histopathological studies, strongly suggest that Ru-3 was almost non-toxic. In addition, the synergistic effect of Ru-3 with common antibiotics such as ampicillin, chloramphenicol, tetracycline, kanamycin and gentamicin on Staphylococcus aureus was detected by chessboard method. Finally, in vivo results revealed that Ru-3 could obviously promote the wound healing of Staphylococcus aureus infected mice.https://www.frontiersin.org/articles/10.3389/fchem.2022.1035741/fullRu(II) complexesantimicrobial propertiesantibiofilm activitysynergistic effectmembrane-disruptive mechanism |
| spellingShingle | Li Jiang Yuanyuan Ma Yanshi Xiong Yanhui Tan Xuemin Duan Xiangwen Liao Jintao Wang Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism Frontiers in Chemistry Ru(II) complexes antimicrobial properties antibiofilm activity synergistic effect membrane-disruptive mechanism |
| title | Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism |
| title_full | Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism |
| title_fullStr | Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism |
| title_full_unstemmed | Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism |
| title_short | Ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against Staphylococcus aureus with membrane-disruptive mechanism |
| title_sort | ruthenium polypyridine complexes with triphenylamine groups as antibacterial agents against staphylococcus aureus with membrane disruptive mechanism |
| topic | Ru(II) complexes antimicrobial properties antibiofilm activity synergistic effect membrane-disruptive mechanism |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.1035741/full |
| work_keys_str_mv | AT lijiang rutheniumpolypyridinecomplexeswithtriphenylaminegroupsasantibacterialagentsagainststaphylococcusaureuswithmembranedisruptivemechanism AT yuanyuanma rutheniumpolypyridinecomplexeswithtriphenylaminegroupsasantibacterialagentsagainststaphylococcusaureuswithmembranedisruptivemechanism AT yanshixiong rutheniumpolypyridinecomplexeswithtriphenylaminegroupsasantibacterialagentsagainststaphylococcusaureuswithmembranedisruptivemechanism AT yanhuitan rutheniumpolypyridinecomplexeswithtriphenylaminegroupsasantibacterialagentsagainststaphylococcusaureuswithmembranedisruptivemechanism AT xueminduan rutheniumpolypyridinecomplexeswithtriphenylaminegroupsasantibacterialagentsagainststaphylococcusaureuswithmembranedisruptivemechanism AT xiangwenliao rutheniumpolypyridinecomplexeswithtriphenylaminegroupsasantibacterialagentsagainststaphylococcusaureuswithmembranedisruptivemechanism AT jintaowang rutheniumpolypyridinecomplexeswithtriphenylaminegroupsasantibacterialagentsagainststaphylococcusaureuswithmembranedisruptivemechanism |