Premium
Synthesis of α‐ and β‐Pyran Naphthoquinones as a New Class of Antitubercular Agents
Author(s) -
Ferreira Sabrina B.,
de Carvalho da Silva Fernando,
Bezerra Flávio A. F. M.,
Lourenço Maria C. S.,
Kaiser Carlos R.,
Pinto Angelo C.,
Ferreira Vitor F.
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900162
Subject(s) - naphthoquinone , chemistry , knoevenagel condensation , pyran , quinone , minimum inhibitory concentration , antibacterial activity , methylene blue , formaldehyde , mycobacterium tuberculosis , ethanol , organic chemistry , in vitro , stereochemistry , tuberculosis , bacteria , biochemistry , biology , medicine , pathology , photocatalysis , genetics , catalysis
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.