title: Novel hybrids of metronidazole and quinolones: synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin.
abstract: A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg(2+) ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex.
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Sheng-Feng
authors.initials: SF
authors.lastname: Cui
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Peng
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Zhang
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Syed
authors.initials: S
authors.lastname: Rasheed
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Kannekanti
authors.initials: K
authors.lastname: Vijaya Kumar
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China. Electronic address: zhouch@swu.edu.cn.
authors.forename: Cheng-He
authors.initials: CH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000187:drug effects; D006801:Humans; D007477:Ions / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry*; D008795:Metronidazole / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D007477:Ions; D015363:Quinolones; D012709:Serum Albumin; D008795:Metronidazole; D004247:DNA; C427203:calf thymus DNA; D008274:Magnesium
keywords: Antibacterial; DNA; HSA; Imidazole; Metronidazole; Quinolone