title: 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.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Milano, via Mangiagalli 25, I-20133 Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Straniero
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Milano, via Mangiagalli 25, I-20133 Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pallavicini
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Milano, via Mangiagalli 25, I-20133 Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Chiodini
authors.affiliation: Department of Medical Biothechnologies and Translational Medicine, Università di Milano, via Vanvitelli 32, I-20129 Milano, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanotto
authors.affiliation: Department of Medical Biothechnologies and Translational Medicine, Università di Milano, via Vanvitelli 32, I-20129 Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Volontè
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università di Milano, via Balzaretti 9, I-2013 Milano, Italy; CNR Institute of Neurosciences, Cellular and Molecular Pharmacology Section, Università di Milano, via Vanvitelli 32, I-20129 Milano, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Radaelli
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Milano, via Mangiagalli 25, I-20133 Milano, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Bolchi
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Milano, via Mangiagalli 25, I-20133 Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fumagalli
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore, largo Gemelli 8, I-00168 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore, largo Gemelli 8, I-00168 Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Menchinelli
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore, largo Gemelli 8, I-00168 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Delogu
authors.affiliation: Institute of Microbiology, Università Cattolica del Sacro Cuore, largo Gemelli 8, I-00168 Rome, Italy.
authors.forename: Basem
authors.initials: B
authors.lastname: Battah
authors.affiliation: Department of Medical Biothechnologies and Translational Medicine, Università di Milano, via Vanvitelli 32, I-20129 Milano, Italy; CNR Institute of Neurosciences, Cellular and Molecular Pharmacology Section, Università di Milano, via Vanvitelli 32, I-20129 Milano, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: De Giuli Morghen
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Milano, via Mangiagalli 25, I-20133 Milano, Italy. Electronic address: ermanno.valoti@unimi.it.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Valoti
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D001555:Benzene Derivatives; D002455:Cell Division / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D055624:Methicillin-Resistant Staphylococcus aureus / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001549:Benzamides; D001555:Benzene Derivatives; C078231:2,6-difluorobenzamide
keywords: 2,6-Difluorobenzamide; Antibacterial activity; Benzodioxane; FtsZ; Methicillin resistance; Mycobacterium tuberculosis; Staphylococcus aureus