title: Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis.
abstract: We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells.
authors.forename: Ben
authors.initials: B
authors.lastname: Gold
authors.forename: Robert
authors.initials: R
authors.lastname: Smith
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Quyen
authors.initials: Q
authors.lastname: Nguyen
authors.forename: Julia
authors.initials: J
authors.lastname: Roberts
authors.forename: Yan
authors.initials: Y
authors.lastname: Ling
authors.forename: Landys
authors.initials: L
authors.lastname: Lopez Quezada
authors.forename: Selin
authors.initials: S
authors.lastname: Somersan
authors.forename: Thulasi
authors.initials: T
authors.lastname: Warrier
authors.forename: David
authors.initials: D
authors.lastname: Little
authors.forename: Maneesh
authors.initials: M
authors.lastname: Pingle
authors.forename: David
authors.initials: D
authors.lastname: Zhang
authors.forename: Elaine
authors.initials: E
authors.lastname: Ballinger
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers, the State University of New Jersey , Newark, New Jersey 07013, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Zimmerman
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers, the State University of New Jersey , Newark, New Jersey 07013, United States.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dartois
authors.forename: Paul
authors.initials: P
authors.lastname: Hanson
authors.forename: Lester A
authors.initials: LA
authors.lastname: Mitscher
authors.forename: Patrick
authors.initials: P
authors.lastname: Porubsky
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Rogers
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Schoenen
authors.forename: Carl
authors.initials: C
authors.lastname: Nathan
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002478:Cells, Cultured; D002511:Cephalosporins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D008862:Microsomes, Liver / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D002511:Cephalosporins