title: Syntheses and antibacterial activity of soluble 9-bromo substituted indolizinoquinoline-5,12-dione derivatives.
abstract: In our previous research, 9-bromo indolizinoquinoline-5,12-dione 1 has been found to be a good anti-MRSA agent. However, it had very low bioavailability in vivo possibly due to its low solubility in water. In order to obtain the derivatives with higher anti-MRSA activity and good water solubility, twenty eight bromo-substituted indolizinoquinoline-5,12-dione derivatives were synthesized in the present study. The antibacterial activity of the synthesized compounds was evaluated against one gram-negative and some gram-positive bacterial strains including 100 clinical MRSA strains. The UV assays were carried out to determine the solubility of six active compounds 16, 21, 23 and 27-29. The most potent compound 28 exhibited strong activity against clinical MRSA strains with both MIC50and MIC90values lower than 7.8 ng/mL. Compound 27 had good water solubility of 1.98 mg/mL and strong activity against clinical MRSA strains with MIC50value of 63 ng/mL and MIC90value of 125 ng/mL, 16-fold higher than that of Vancomycin.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Hao-Wen
authors.initials: HW
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Teng-Wei
authors.initials: TW
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Le-Mao
authors.initials: LM
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
authors.forename: Lu-Xia
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address: lssalk@mail.sysu.edu.cn.
authors.forename: Lin-Kun
authors.initials: LK
authors.lastname: An
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D008826:Microbial Sensitivity Tests; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; D014867:Water
keywords: Antibacterial; Indolizinoquinolinedione; Methicillin-resistant Staphylococcus aureus; Multi-drug resistance; Quinone