Synthesis and Antimicrobial Activity of 4-Chloro-3-Nitrophenylthiourea Derivatives Targeting Bacterial Type II Topoisomerases

Chemical Biology & Drug Design
Anna BielenicaMarta Struga

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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Citations

Apr 24, 2017·Chemical Biology & Drug Design·Anna BielenicaGabriele Giliberti
Feb 8, 2019·Physical Chemistry Chemical Physics : PCCP·Vinicius T SantanaOtaciro R Nascimento
Sep 27, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna BielenicaMarta Struga
Oct 23, 2018·European Journal of Medicinal Chemistry·Barbara ParrinoStella Cascioferro

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