Synthesis and Antimicrobial Activity of 4‐Chloro‐3‐Nitrophenylthiourea Derivatives Targeting Bacterial Type II Topoisomerases |
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| Authors: | Anna Bielenica Karolina Stępień Agnieszka Napiórkowska Ewa Augustynowicz‐Kopeć Sylwester Krukowski Marta Włodarczyk Marta Struga |
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| Affiliation: | 1. Chair and Department of Biochemistry, Medical University, Warszawa, Poland;2. Department of Pharmaceutical Microbiology, Medical University, Warszawa, Poland;3. Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warszawa, Poland;4. Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Medical University, Warszawa, Poland;5. Department of Pharmacogenomics, Faculty of Pharmacy, Medical University, Warszawa, Poland |
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| 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. |
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| Keywords: | antimicrobial activity antitubercular activity biofilm thiourea derivatives topoisomerase |
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