title: Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents.
abstract: Series ofN-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistantStaphylococcus aureus(MRSA) agents from a molecular hybridization approach. The representative compound19showed an MIC = 1 μg/mL against a panel of MRSA clinical isolates as it possessed comparablein vitroactivities to that of vancomycin. Moreover, compound19also exhibited MIC = 1 μg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistantEnterococcus faecalis(VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound19was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of newN-substituted carbazoles as potential anti-MRSA agents.
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Tsai-Ling Yang
authors.initials: TY
authors.lastname: Lauderdale
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Guann-Yi
authors.initials: GY
authors.lastname: Yu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Jinq-Chyi
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Yi-Wun
authors.initials: YW
authors.lastname: Jhang
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Chien-Huang
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Ke
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Amit A
authors.initials: AA
authors.lastname: Sadani
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Yeh
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Huang
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Kuo
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: De-Jiun
authors.initials: DJ
authors.lastname: Tsai
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Chen-Tso
authors.initials: CT
authors.lastname: Tseng
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Lun K
authors.initials: LK
authors.lastname: Tsou
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research and National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , Miaoli County 35053, Taiwan , R.O.C.
authors.forename: Kak-Shan
authors.initials: KS
authors.lastname: Shia
keywords: Methicillin-resistant Staphylococcus aureus; carbazole derivatives; molecular hybridization; resistant bacteria; vancomycin