title: Synthesis and Antimicrobial Activity of 4-Chloro-3-Nitrophenylthiourea Derivatives Targeting Bacterial Type II Topoisomerases.
abstract: A series of novel 4-chloro-3-nitrophenylthiourea derivatives were synthesized and evaluated for their antimicrobial, antibiofilm and tuberculostatic activities. Most of compounds exhibited high antibacterial activity against both standard and hospital strains (MIC values 0.5-2 μg/mL), as compared to Ciprofloxacin. Derivatives with 3,4-dichlorophenyl (11) and 3-chloro-4-methylphenyl (13) substituents were the most promising towards Gram-positive pathogens. Both of them exhibited antibiofilm potency and effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis. Two N-alkylthioureas (20, 21) showed twofold to fourfold increase in in vitro potency against isolates of Mycobacterium tuberculosis, as compared to Isoniazid. An action of 7, 10, 11, 13, 20 and 21 against activity of topoisomerases isolated from Staphylococcus aureus was studied. Synthesized compounds were found as non-genotoxic.
authors.affiliation: Chair and Department of Biochemistry, Medical University, 02-097, Warszawa, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bielenica
authors.affiliation: Department of Pharmaceutical Microbiology, Medical University, 02-007, Warszawa, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Stępień
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138, Warszawa, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Napiórkowska
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138, Warszawa, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
authors.affiliation: Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Medical University, 02-097, Warszawa, Poland.
authors.forename: Sylwester
authors.initials: S
authors.lastname: Krukowski
authors.affiliation: Department of Pharmacogenomics, Faculty of Pharmacy, Medical University, 02-097, Warszawa, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Włodarczyk
authors.affiliation: Department of Pharmacogenomics, Faculty of Pharmacy, Medical University, 02-097, Warszawa, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Struga
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D013212:Staphylococcus epidermidis / Q000502:physiology*; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II; D013890:Thiourea
keywords: antimicrobial activity; antitubercular activity; biofilm; thiourea derivatives; topoisomerase