title: Antibacterial activity of quinoxalines, quinazolines, and 1,5-naphthyridines.
abstract: Several phenyl substituted naphthalenes and isoquinolines have been identified as antibacterial agents that inhibit FtsZ-Zing formation. In the present study we evaluated the antibacterial of several phenyl substituted quinoxalines, quinazolines and 1,5-naphthyridines against methicillin-sensitive and methicillin-resistant Staphylococcusaureus and vancomycin-sensitive and vancomycin-resistant Enterococcusfaecalis. Some of the more active compounds against S. aureus were evaluated for their effect on FtsZ protein polymerization. Further studies were also performed to assess their relative bactericidal and bacteriostatic activities. The notable differences observed between nonquaternized and quaternized quinoxaline derivatives suggest that differing mechanisms of action are associated with their antibacterial properties.
authors.affiliation: Department of Medicinal Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Parhi
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Saionz
authors.forename: Padmanava
authors.initials: P
authors.lastname: Pradhan
authors.forename: Malvika
authors.initials: M
authors.lastname: Kaul
authors.forename: Kalkal
authors.initials: K
authors.lastname: Trivedi
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pilch
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: LaVoie
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D009287:Naphthyridines; D011799:Quinazolines; D011810:Quinoxalines; D014640:Vancomycin
keywords: 1,5-Naphthyridines; Antibiotics; Bactericidal; Bacteriostatic; Enterococcus faecalis; Quinazolines; Quinoxalines; Staphylococcus aureus
references.citation: Biochemistry. 2005 May 31;44(21):7879-84
references.pmid: 15910002
references.citation: Nat Rev Microbiol. 2009 Sep;7(9):642-53
references.pmid: 19680248
references.citation: J Med Chem. 2010 May 27;53(10):3927-36
references.pmid: 20426423
references.citation: Expert Opin Ther Targets. 2009 Sep;13(9):1037-51
references.pmid: 19659446
references.citation: Science. 2008 Sep 19;321(5896):1673-5
references.pmid: 18801997
references.citation: J Med Chem. 2012 Nov 26;55(22):10160-76
references.pmid: 23050700
references.citation: ChemMedChem. 2009 Feb;4(2):249-60
references.pmid: 19115304
references.citation: Curr Biol. 2005 Jul 12;15(13):R514-26
references.pmid: 16005287
references.citation: Nat Rev Drug Discov. 2008 Apr;7(4):324-38
references.pmid: 18323848
references.citation: Clin Microbiol Infect. 2009 Mar;15(3):224-31
references.pmid: 19335370
references.citation: Lancet Infect Dis. 2010 Sep;10(9):597-602
references.pmid: 20705517
references.citation: Bioorg Med Chem Lett. 2013 Apr 1;23(7):2001-6
references.pmid: 23481648
references.citation: Bioorg Med Chem Lett. 2012 Nov 15;22(22):6962-6
references.pmid: 23058886
references.citation: Biochemistry. 2011 Sep 13;50(36):7719-34
references.pmid: 21823588
references.citation: Org Lett. 2005 Dec 8;7(25):5609-12
references.pmid: 16321003
references.citation: Nature. 1991 Nov 14;354(6349):161-4
references.pmid: 1944597
references.citation: Future Med Chem. 2010 Aug;2(8):1305-23
references.pmid: 21339840
references.citation: Expert Opin Ther Pat. 2011 May;21(5):657-79
references.pmid: 21413908
references.citation: Microbiol Mol Biol Rev. 2010 Dec;74(4):504-28
references.pmid: 21119015
references.citation: Clin Microbiol Infect. 2009 Mar;15(3):209-11
references.pmid: 19335367
references.citation: Biochemistry. 2005 Dec 20;44(50):16584-93
references.pmid: 16342949
references.citation: J Med Chem. 1981 Jan;24(1):93-101
references.pmid: 6451700
references.citation: Eur J Med Chem. 2013 Feb;60:395-409
references.pmid: 23314053
references.citation: ACS Chem Biol. 2012 Feb 17;7(2):269-77
references.pmid: 22047077
references.citation: Bioorg Med Chem. 2012 Dec 15;20(24):7012-29
references.pmid: 23127490
references.citation: Clin Microbiol Infect. 2009 Mar;15(3):218-23
references.pmid: 19335369
references.citation: J Antimicrob Chemother. 2009 Sep;64 Suppl 1:i29-36
references.pmid: 19675016
references.citation: Biochemistry. 2008 Mar 11;47(10):3225-34
references.pmid: 18275156
references.citation: J Med Chem. 2011 Jan 13;54(1):374-81
references.pmid: 21126020
references.citation: J Biol Chem. 2010 May 7;285(19):14239-46
references.pmid: 20212044
references.citation: JAMA. 2007 Oct 17;298(15):1763-71
references.pmid: 17940231