title: Synthesis of alpha- and beta-pyran naphthoquinones as a new class of antitubercular agents.
abstract: A series of alpha- and beta-pyran naphthoquinones (lapachones) have been synthesized and evaluated for their in-vitro antibacterial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar-Blue susceptibility test; the activity was expressed as the minimum inhibitory concentration (MIC) in microg/mL. The synthetic methodology consisted of the formation of methylene and aryl o-quinone methides (o-QMs) generated by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with formaldehyde and arylaldehydes. These o-QMs then undergo facile hetero Diels-Alder reactions with dienophiles in aqueous ethanol media. Some naphthoquinones exhibited inhibition with MIC values of 1.25 microg/mL, similar to that of pharmaceutical concentrations currently used in tuberculosis treatment. These results justify further research into the value of these quinones as part of an original treatment for tuberculosis.
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Química, LABRMN, Rio de Janeiro, Brazil.
authors.forename: Sabrina B
authors.initials: SB
authors.lastname: Ferreira
authors.forename: Fernando
authors.initials: F
authors.lastname: de Carvalho da Silva
authors.forename: Flávio A F M
authors.initials: FA
authors.lastname: Bezerra
authors.forename: Maria C S
authors.initials: MC
authors.lastname: Lourenço
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Kaiser
authors.forename: Angelo C
authors.initials: AC
authors.lastname: Pinto
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D009285:Naphthoquinones