title: Synthesis, structure, and antibacterial activity of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid and 4-oxo-1, 4-dihydrocinnoline-3-carboxylic acid derivatives as isosteric analogues of quinolones.
abstract: Chemical modification of cinnoxacin was studied with the aim of improving its antibacterial activity and spectrum. A series of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid derivatives was synthesized and their in vitro antibacterial activity was evaluated. These derivatives were designed as isosteric analogues of fluoroquinolones and are characterized by the presence of an imine group instead of an oxo group at the 4-position and a nitrogen atom in position 2. The crystal structure of one analogue determined by X-ray diffraction shows the dipolar form of the compound in the solid state. The in vitro antibacterial activity of the synthesized compounds against Gram-positive and Gram-negative bacteria was examined. The MIC of the most active compounds lies in the range of the first generation of quinolones such as nalidixic acid. The compounds with dichlorobenzyl substituent show enhanced activity against Gram-positive bacteria.
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Medical University of Łódz, Poland. stanczak@pharm.am.lodz.pl
authors.forename: Andrzej
authors.initials: A
authors.lastname: Stańczak
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Ochocki
authors.forename: Dariusz
authors.initials: D
authors.lastname: Martynowski
authors.forename: Marek
authors.initials: M
authors.lastname: Główka
authors.forename: Ewa
authors.initials: E
authors.lastname: Nawrot
mesh_terms: D042462:4-Quinolones; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
chemical_list: D042462:4-Quinolones; D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D059004:Topoisomerase I Inhibitors