title: Antimicrobial activity of a ferrocene-substituted carborane derivative targeting multidrug-resistant infection.
abstract: Multidrug resistance (MDR) of bacteria is still an unsolved serious problem to threaten the health of human beings. Developing new antibacterial agents, therefore, are urgently needed. Herein, we have explored the possibility to design and synthesize some novel antibacterial agents including ferrocene-substituted carborane derivative (Fc(2)SBCp(1)) and have evaluated the relevant antibacterial action against two clinical common MDR pathogens (i.e., Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa) in vitro and in vivo. The results demonstrate that in vitro antimicrobial activity of Fc(2)SBCp(1) could be gradually transformed into a bactericidal effect from a bacteriostatic effect with the increasing concentration of the active carborane derivative, which can also prevent biofilm formation at concentrations below MIC (i.e., minimal inhibitory concentration). Biocompatibility studies indicate that there exists no/or little toxic effect of Fc(2)SBCp(1) on normal cells/tissues and leads to little hemolysis. In vivo studies illustrate that the new carborane derivative Fc(2)SBCp(1) is highly effective in treating bacteremia caused by S. aureus and P. aeruginosa as well as interstitial pneumonia caused by S. aureus. This raises the possibility for the potential utilization of the new ferrocene-substituted carborane derivatives as promising antibacterial therapeutic agents against MDR bacterial infections in future clinical applications.
authors.affiliation: State Key Laboratory of Bioelectronics (Chien-Shiung Wu Lab), Southeast University, Nanjing 210096, China.
authors.forename: Shuihong
authors.initials: S
authors.lastname: Li
authors.forename: Zhaojin
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Wei
authors.forename: Changyu
authors.initials: C
authors.lastname: Wu
authors.forename: Shengping
authors.initials: S
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Xinqing
authors.initials: X
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D016470:Bacteremia / Q000188:drug therapy* / Q000473:pathology; D018407:Bacterial Physiological Phenomena / Q000187:drug effects; D001880:Boranes / Q000008:administration & dosage* / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D000075163:Metallocenes; D051379:Mice; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001880:Boranes; D005296:Ferrous Compounds; D000075163:Metallocenes; D002244:Carbon; C004998:ferrocene