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Synthesis of α‐ and β‐Pyran Naphthoquinones as a New Class of Antitubercular Agents |
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| Authors: | Sabrina B. Ferreira Fernando de Carvalho da Silva Flávio A. F. M. Bezerra Maria C. S. Lourenço Carlos R. Kaiser Angelo C. Pinto Vitor F. Ferreira |
| Affiliation: | 1. Universidade Federal do Rio de Janeiro, Instituto de Química, LABRMN, Rio de Janeiro, Brazil;2. Universidade Federal Fluminense, Instituto de Química, Departamento de Química Organica, Campus do Valonguinho, CEG, Niterói, Brazil. Fax: +55 21 262‐923‐62;3. Funda??o Oswaldo Cruz, Instituto de Pesquisa Clínica Evandro Chagas – IPEC, Laboratório de Bacteriologia e Bioensaios em Micobactérias, Rio de Janeiro, Brazil |
| Abstract: | A series of α‐ and β‐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 μg/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 μg/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. |
| Keywords: | Lapachones Naphthoquinones Synthesis Tuberculostatics |