title: Biological evaluation of bisbenzaldehydes against four Mycobacterium species.
abstract: A series of bisbenzaldehydes and structurally related analogs, conveniently synthesized via microwave-assisted reactions, were evaluated in vitro against drug susceptible and multi-drug resistant Mycobacterium tuberculosis, against virulent Mycobacterium bovis, against Mycobacterium ulcerans and against two Mycobacterium avium subspecies. Among the 33 substances that were tested, compound 12, i.e. 4,4'-[1,12-dodecanediyl(oxy)]bisbenzaldehyde, emerged as the most promising hit. Its activity was further confirmed in an intracellular growth inhibition assay of M. tb in murine J774 A.1 macrophages. None of the compounds showed significant cytotoxicity on human C3A hepatocytes in a neutral red dye uptake assay and no genotoxicity or mutagenicity was observed as demonstrated by a VITOTOX™ test and confirmed with a comet assay.
authors.affiliation: Program Host-Pathogen Interactions, Service Immunology, O.D. Communicable & Infectious Diseases, Scientific Institute of Public Health WIV-ISP (Site Ukkel), Engelandstraat 642, B-1180 Ukkel, Belgium.
authors.forename: Davie
authors.initials: D
authors.lastname: Cappoen
authors.forename: Delphine
authors.initials: D
authors.lastname: Forge
authors.forename: Frank
authors.initials: F
authors.lastname: Vercammen
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mathys
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kiass
authors.forename: Virginie
authors.initials: V
authors.lastname: Roupie
authors.forename: Roel
authors.initials: R
authors.lastname: Anthonissen
authors.forename: Luc
authors.initials: L
authors.lastname: Verschaeve
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Vanden Eynde
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009161:Mycobacterium / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D009162:Mycobacterium avium / Q000187:drug effects / Q000502:physiology; D009163:Mycobacterium bovis / Q000187:drug effects / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology; D019911:Mycobacterium ulcerans / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity
chemical_list: C584489:4,4'-(1,12-dodecanediyl(oxy))bisbenzaldehyde; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001547:Benzaldehydes