title: Structure-activity relationships of 2-benzylsulfanylbenzothiazoles: synthesis and selective antimycobacterial properties.
abstract: A set of 2-benzylsulfanyl derivatives of benzothiazole was synthesized and evaluated for antimicrobial and cytotoxic activities. The biological screening on antimicrobial activity against a panel of Gram-positive and Gram-negative bacteria, yeasts and fungi identified benzylsulfanyl derivatives of benzothiazole as selective inhibitors of mycobacteria. The lead compounds in the set, dinitro derivatives exhibited significant activity against sensitive and multidrug-resistant strains of M. tuberculosis and low cytotoxicity. The QSAR study indicated that the antituberculotic activity is connected with LUMO and HOMO energies. The lower lipophilicity and the increased size of the molecule contribute to antituberculotic activity. Thus, dinitrobenzylsulfanyl derivatives of benzothiazole represent promising smallmolecule synthetic antimycobacterials.
authors.affiliation: Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic. vera.klimesova@faf.cuni.cz
authors.forename: Vĕra
authors.initials: V
authors.lastname: Klimesová
authors.forename: Jan
authors.initials: J
authors.lastname: Koci
authors.forename: Karel
authors.initials: K
authors.lastname: Palát
authors.forename: Jirina
authors.initials: J
authors.lastname: Stolariková
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Dahse
authors.forename: Ute
authors.initials: U
authors.lastname: Möllmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D013440:Sulfides