3-(Benzodioxan-2-ylmethoxy)-2,6-difluorobenzamides bearing hydrophobic substituents at the 7-position of the benzodioxane nucleus potently inhibit methicillin-resistant Sa and Mtb cell division

Lipophilic substituents at benzodioxane C (7) of 3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamide improve the antibacterial activity against methicillin-resistant Staphylococcus aureus strains to MIC values in the range of 0.2–2.5 μg/mL, whereas hydrophilic substituents at the same position and mod...

Full description

Saved in:
Bibliographic Details
Published in:European journal of medicinal chemistry 2016-09, Vol.120, p.227-243
Main Authors: Straniero, Valentina, Pallavicini, Marco, Chiodini, Giuseppe, Zanotto, Carlo, Volontè, Luca, Radaelli, Antonia, Bolchi, Cristiano, Fumagalli, Laura, Sanguinetti, Maurizio, Menchinelli, Giulia, Delogu, Giovanni, Battah, Basem, De Giuli Morghen, Carlo, Valoti, Ermanno
Format: Article
Language:English
Subjects:
2,6-Difluorobenzamide
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibacterial activity
Benzamides - chemistry
Benzamides - pharmacology
Benzene Derivatives
Benzodioxane
Cell Division - drug effects
FtsZ
Hydrophobic and Hydrophilic Interactions
Methicillin resistance
Methicillin-Resistant Staphylococcus aureus - cytology
Methicillin-Resistant Staphylococcus aureus - drug effects
Mycobacterium tuberculosis
Staphylococcus aureus
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lipophilic substituents at benzodioxane C (7) of 3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamide improve the antibacterial activity against methicillin-resistant Staphylococcus aureus strains to MIC values in the range of 0.2–2.5 μg/mL, whereas hydrophilic substituents at the same position and modifications at the benzodioxane substructure, excepting for replacement with 2-cromanyl, are deleterious. Some of the lead compounds also exhibit good activity against Mtb. Parallel SARs to those of 3-(2-benzothiazol-2-ylmethoxy)-2,6-difluorobenzamide, well known FtsZ inhibitor, and cells alterations typical of FtsZ inhibition indicate such a protein as the target of these potent antibacterial benzodioxane-benzamides. [Display omitted] •The antibacterial 3-(1,4-benzodioxan-2-yl)-2,6-difluorobenzamide was modified.•Lipophilic substituents at benzodioxane C(7) increase activity to
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2016.03.068