title: Antimycobacterial and photosynthetic electron transport inhibiting activity of ring-substituted 4-arylamino-7-chloroquinolinium chlorides.
abstract: In this study, a series of twenty-five ring-substituted 4-arylamino-7-chloroquinolinium chlorides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts and also primary in vitro screening of the synthesized compounds was performed against mycobacterial species. 4-[(2-Bromophenyl)amino]-7-chloroquinolinium chloride showed high biological activity against M. marinum, M. kansasii, M. smegmatis and 7-chloro-4-[(2-methylphenyl)amino]quinolinium chloride demonstrated noteworthy biological activity against M. smegmatis and M. avium subsp. paratuberculosis. The most effective compounds demonstrated quite low toxicity (LD₅₀ > 20 μmol/L) against the human monocytic leukemia THP-1 cell line within preliminary in vitro cytotoxicity screening. The tested compounds were found to inhibit PET in photosystem II. The PET-inhibiting activity expressed by IC₅₀ value of the most active compound 7-chloro-4-[(3-trifluoromethylphenyl)amino]quinolinium chloride was 27 μmol/L and PET-inhibiting activity of ortho-substituted compounds was significantly lower than this of meta- and para-substituted ones. The structure-activity relationships are discussed for all compounds.
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Otevrel
authors.forename: Pavel
authors.initials: P
authors.lastname: Bobal
authors.forename: Iveta
authors.initials: I
authors.lastname: Zadrazilova
authors.forename: Rodney
authors.initials: R
authors.lastname: Govender
authors.forename: Matus
authors.initials: M
authors.lastname: Pesko
authors.forename: Stanislava
authors.initials: S
authors.lastname: Keltosova
authors.forename: Petra
authors.initials: P
authors.lastname: Koleckarova
authors.forename: Petr
authors.initials: P
authors.lastname: Marsalek
authors.forename: Ales
authors.initials: A
authors.lastname: Imramovsky
authors.forename: Aidan
authors.initials: A
authors.lastname: Coffey
authors.forename: Jim
authors.initials: J
authors.lastname: O'Mahony
authors.forename: Peter
authors.initials: P
authors.lastname: Kollar
authors.forename: Alois
authors.initials: A
authors.lastname: Cizek
authors.forename: Katarina
authors.initials: K
authors.lastname: Kralova
authors.forename: Josef
authors.initials: J
authors.lastname: Jampilek
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000138:chemical synthesis / Q000494:pharmacology; D002736:Chloroplasts / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects; D010788:Photosynthesis / Q000187:drug effects; D011806:Quinolinium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D012995:Solubility; D018724:Spinacia oleracea / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D002712:Chlorides; D011806:Quinolinium Compounds