title: Discovery of novel berberine imidazoles as safe antimicrobial agents by down regulating ROS generation.
abstract: A series of novel berberine-based imidazole derivatives as new type of antimicrobial agents were developed and characterized. Most of them gave good antibacterial activity toward the Gram-positive and negative bacteria. Noticeably, imidazolyl berberine 3a exhibited low MIC value of 1μg/mL against Eberthella typhosa, which was even superior to reference drugs berberine, chloromycin and norfloxacin. The cell toxicity and ROS generation assay indicated that compound 3a showed low cell toxicity. The interactive investigation by UV-vis spectroscopic method revealed that compound 3a could effectively intercalate into calf thymus DNA to form 3a-DNA complex which might further block DNA replication to exert the powerful antimicrobial activities. The binding behavior of compound 3a to DNA topoisomerase IB revealed that hydrogen bonds and electrostatic interactions played important roles in the association of compound 3a with DNA topoisomerase IB.
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Wen
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Ponmani
authors.initials: P
authors.lastname: Jeyakkumar
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Srinivasa Rao
authors.initials: SR
authors.lastname: Avula
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China. Electronic address: zhouch@swu.edu.cn.
authors.forename: Cheng-He
authors.initials: CH
authors.lastname: Zhou
mesh_terms: 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; D001599:Berberine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D055808:Drug Discovery; D005658:Fungi / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D007093:Imidazoles; D017382:Reactive Oxygen Species; D001599:Berberine
keywords: Antimicrobial; Berberine; DNA; Imidazole; ROS