TY - JOUR
T1 - 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
AU - Straniero, Valentina
AU - Pallavicini, Marco
AU - Chiodini, Giuseppe
AU - Zanotto, Carlo
AU - Volontè, Luca
AU - Radaelli, Antonia
AU - Bolchi, Cristiano
AU - Fumagalli, Laura
AU - Sanguinetti, Maurizio
AU - Menchinelli, Giulia
AU - Delogu, Giovanni
AU - Battah, Basem
AU - De Giuli Morghen, Carlo
AU - Valoti, Ermanno
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - 2,6-Difluorobenzamide
KW - Antibacterial activity
KW - Benzodioxane
KW - FtsZ
KW - Methicillin resistance
KW - Mycobacterium tuberculosis
KW - Staphylococcus aureus
KW - 2,6-Difluorobenzamide
KW - Antibacterial activity
KW - Benzodioxane
KW - FtsZ
KW - Methicillin resistance
KW - Mycobacterium tuberculosis
KW - Staphylococcus aureus
UR - http://hdl.handle.net/10807/80014
U2 - 10.1016/j.ejmech.2016.03.068
DO - 10.1016/j.ejmech.2016.03.068
M3 - Article
SN - 0223-5234
VL - 120
SP - 227
EP - 243
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -
