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Synthesis, biological activity, and evaluation of the mode of action of novel antitubercular benzofurobenzopyrans substituted on A ring

Authors :
Termentzi, Aikaterini
Khouri, Inana
Gaslonde, Thomas
Prado, Soizic
Saint-Joanis, Brigitte
Bardou, Fabienne
Amanatiadou, Elsa P.
Vizirianakis, Ioannis S.
Kordulakova, Jana
Jackson, Mary
Brosch, Roland
Janin, Yves L.
Daffé, Mamadou
Tillequin, François
Michel, Sylvie
Source :
European Journal of Medicinal Chemistry. Dec2010, Vol. 45 Issue 12, p5833-5847. 15p.
Publication Year :
2010

Abstract

Abstract: The 8-, 9-, 10-, and 11-halo, hydroxy, and methoxy derivatives of the antimycobacterial 3,3-dimethyl-3H-benzofuro[3,2-f][1]benzopyran were synthesized by condensation of the diazonium salts of 2-chloroanilines (13–17) with 1,4-benzoquinone (18), reduction of the intermediate phenylbenzoquinones 19–22 to dihydroxybiphenyls, cyclisation to halo-2-hydroxydibenzofurans 24–27, and construction of the pyran ring by thermal rearrangement of the corresponding dimethylpropargyl ethers 35–38. Palladium catalyzed nucleophilic aromatic substitution permitted conversion of the halo to the corresponding hydroxy derivatives which were methylated to methoxy-3,3-dimethyl-3H-benzofuro[3,2-f][1]benzopyran. All compounds substituted on the A ring were found more potent than the reference compound 1 against Mycobacterium bovis BCG and the virulent strain Mycobacterium tuberculosis H37Rv. The effect of the most active derivatives on mycolate synthesis was explored in order to confirm the preliminary hypothesis of an effect on mycobacterial cell wall biosynthesis. The linear 9-methoxy-2,2-dimethyl-2H-benzofuro[2,3-g][1]benzopyran (46) exhibiting a good antimycobacterial activity and devoid of cytotoxicity appeared to be the most promising compound. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02235234
Volume :
45
Issue :
12
Database :
Academic Search Index
Journal :
European Journal of Medicinal Chemistry
Publication Type :
Academic Journal
Accession number :
55378743
Full Text :
https://doi.org/10.1016/j.ejmech.2010.09.048