title: Biological evaluation of tetracationic compounds based on two 1,4-diazabicyclo[2.2.2]octane moieties connected by different linkers.
abstract: A series of 1,4-diazabicyclo[2.2.2]octane derivatives differing by linker moiety was evaluated for activity against several strains of both Gram-positive and Gram-negative bacteria including drug-resistant strains, one strain of fungus and influenza virus A/Puerto Rico/8/34 (H1N1). All compounds exhibited high antibacterial activity against all bacteria except Proteus vulgaris. The minimum inhibitory concentrations (MICs) of compound 1c with an o-phenylenebismethyl linker and compound 1e with a propylene aliphatic linker were found to be low and were comparable or better to the reference drug ciprofloxacin for Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, a time-kill assay was performed to examine the bactericidal kinetics. Compounds 1c and 1e displayed rapid killing effects against St. aureus and Ps. aeruginosa after 2h. Furthermore, compounds 1a-c with aromatic linkers and compound 1e showed the highest antiviral activity.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrent'ev Ave. 8, Novosibirsk 630090, Russia. Electronic address: kat7@ngs.ru.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Burakova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrent'ev Ave. 8, Novosibirsk 630090, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Saranina
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrent'ev Ave. 8, Novosibirsk 630090, Russia.
authors.forename: Nina V
authors.initials: NV
authors.lastname: Tikunova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrent'ev Ave. 8, Novosibirsk 630090, Russia.
authors.forename: Zhanna K
authors.initials: ZK
authors.lastname: Nazarkina
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrent'ev Ave. 8, Novosibirsk 630090, Russia.
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Laktionov
authors.affiliation: Influenza Research Institute, Prof. Popova Str. 15/17, St. Petersburg 197376, Russia.
authors.forename: Lubov' A
authors.initials: LA
authors.lastname: Karpinskaya
authors.affiliation: Influenza Research Institute, Prof. Popova Str. 15/17, St. Petersburg 197376, Russia.
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Anikin
authors.affiliation: Influenza Research Institute, Prof. Popova Str. 15/17, St. Petersburg 197376, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Zarubaev
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrent'ev Ave. 8, Novosibirsk 630090, Russia.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Silnikov
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects; D007700:Kinetics; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000998:Antiviral Agents; D002412:Cations; D010879:Piperazines; C007306:triethylenediamine
keywords: 1,4-Diazabicyclo[2.2.2]octane (DABCO); Antimicrobial activity; Antiviral activity; Cytotoxicity; Quaternary ammonium compounds (QACs)