title: Synthesis, antibacterial and anti-MRSA activity, in vivo toxicity and a structure-activity relationship study of a quinoline thiourea.
abstract: We report the synthesis, antibacterial evaluation of a series of thiourea-containing compounds. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)-((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea 5, was the most active against a range of Gram-positive and Gram-negative bacteria, and exhibited bacteriostatic activity against methicillin resistant Staphylococcus aureus (MRSA) comparable to that of the well-known antibacterial agent vancomycin. Quinoline thiourea 5 was subjected to a detailed structure-activity relationship study, with 5 and its derivatives evaluated for their bacteriostatic activity against both Gram-negative and Gram-positive bacteria. A number of structural features important for the overall activity of quinoline thiourea 5 have been identified. A selection of compounds, including 5, was also evaluated for their in vivo toxicity using the larvae of the Greater wax moth, Galleria mellonella. Compound 5, and a number of derivatives, were found to be non-toxic to the larvae of Galleria mellonella. A new class of antibiotic can result from the further development of this family of compounds.
authors.affiliation: Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: Dolan
authors.affiliation: Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Declan P
authors.initials: DP
authors.lastname: Gavin
authors.affiliation: Department of Microbiology, Pharmacy College, Zawia University, Zawia, Libya.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Eshwika
authors.affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kavanagh
authors.affiliation: Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: McGinley
authors.affiliation: Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: John C
authors.initials: JC
authors.lastname: Stephens
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; D014640:Vancomycin; C037219:quinoline; D013890:Thiourea
keywords: Antibacterial; MRSA; Quinoline; Structure activity relationship; Thiourea