title: Novel benzimidazolyl tetrahydroprotoberberines: Design, synthesis, antimicrobial evaluation and multi-targeting exploration.
abstract: A series of novel benzimidazolyl tetrahydroprotoberberines were conveniently designed and efficiently synthesized from berberine via direct cyclization of tetrahydroprotoberberine aldehyde and o-phenylene diamines under metal-free aerobic oxidation. All the new compounds were characterized by IR,1H NMR,13C NMR and HRMS spectra. The antimicrobial evaluation revealed that the 5-fluorobenzimidazolyl derivative 5b was the most active antibacterial and antifungal molecule with broad spectrum in comparison to Berberine, Chloromycin, Norfloxacin and Fluconazole. It triggered almost no resistance development against MRSA even after 15 passages. Further studies demonstrated that compound 5b could not only effectively interact with Topo IA by hydrogen bonds, but also intercalate into calf thymus DNA and cleave pBR322 DNA, which might be responsible for its powerful bioactivities.
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, 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, China.
authors.forename: Han-Bo
authors.initials: HB
authors.lastname: Liu
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, China.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Gopala
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, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: School of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun 558000, China. Electronic address: peng0703@sgmtu.edu.cn.
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Peng
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, China.
authors.forename: Rong-Xia
authors.initials: RX
authors.lastname: Geng
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, China. Electronic address: zhouch@swu.edu.cn.
authors.forename: Cheng-He
authors.initials: CH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000378:metabolism; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009181:Mycoses / Q000188:drug therapy
chemical_list: D000890:Anti-Infective Agents; D001562:Benzimidazoles; D001600:Berberine Alkaloids; C014845:berbine; D004247:DNA; C427203:calf thymus DNA
keywords: Antibacterial; Antifungal; Benzimidazole; DNA; Tetrahydroprotoberberine