title: Design, synthesis and evaluation of acridine and fused-quinoline derivatives as potential anti-tuberculosis agents.
abstract: The synthesis of twelve acridine and polycyclic acridine derivatives prepared via the Friedländer reaction is described. The one-pot reactions of 2-amino-5-chloro or 5-nitro-benzophenones and a variety of cyclanones and indanones were carried out in a MW oven under TFA catalysis in good yields. The products were designed according natural antituberculosis products and were evaluated for growth inhibitory activity towards Mycobacterium tuberculosis H37Rv (Mtb) through the National Institute of Allergy and Infectious Diseases (NIAID, USA). Three of them underwent additional testings. The cyclopenta[b]quinoline derivative 9 and the acridine derivative 13 showed remarkable MIC values against the rifampin resistant strain. The former exhibited bactericidal activity at 50 μg/mL, its intracellular activity is similar to rifampin and it was not cytotoxic at low concentrations so it can be considered a new lead compound.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAB Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Gisela C
authors.initials: GC
authors.lastname: Muscia
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAB Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Graciela Y
authors.initials: GY
authors.lastname: Buldain
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAB Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: elizabet@ffyb.uba.ar.
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Asís
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003500:Cyclization; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000166:Acridines; D000995:Antitubercular Agents; D011804:Quinolines
keywords: Acridine derivatives; Friedländer synthesis; Inhibitor; Mycobacterium tuberculosis