title: Antimicrobial and Anti-biofilm Activity of Thiourea Derivatives Bearing 3-amino-1H-1,2,4-triazole Scaffold.
abstract: A set of 21 thiourea derivatives were prepared through reacting 3-amino-1H-1,2,4-triazole with the commercial aliphatic and aromatic isothiocyanates. The aliphatic isothiocyanate was used as reagent leading to substitution on NH atom of 3-aminotriazole ring, whereas the triazole amino group was substituted when isothiocyanate group was bonded to the Csp2 hybridized atom, e.g. an aryl or C=O fragment. All compounds were evaluated in vitro for the antimicrobial activity. The derivatives 1, 2, 4, 8, 9, 10 and 12 showed the highest inhibition against Gram-positive cocci (S. aureus and S. epidermidis). The observed MIC values were in the range of 4-32 μg/mL. Compounds were also tested for their in vitro antimicrobial activity against the hospital methicillin-resistant strains of S. aureus. The observed MIC values varied from 4 to 64 μg/mL. The products 4 and 10 effectively inhibited the formation of biofilms of the methicillin-resistant and standard strains of S. epidermidis. The compound 10 was found to be more promising with IC50 values of 2-6 μg/mL as compared to the control. Moreover, the cytotoxicity against the MT-4 cells of all studied thioureas was evaluated. The compound 18 was significantly cytotoxic (CC50 = 8 μM).
authors.forename: Joanna
authors.initials: J
authors.lastname: Stefanska
authors.forename: Karolina
authors.initials: K
authors.lastname: Stepien
authors.forename: Anna
authors.initials: A
authors.lastname: Bielenica
authors.forename: Daniel
authors.initials: D
authors.lastname: Szulczyk
authors.forename: Barbara
authors.initials: B
authors.lastname: Miroslaw
authors.forename: Anna E
authors.initials: AE
authors.lastname: Koziol
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sanna
authors.forename: Filippo
authors.initials: F
authors.lastname: Iuliano
authors.forename: Silvia
authors.initials: S
authors.lastname: Madeddu
authors.forename: Michal
authors.initials: M
authors.lastname: Jozwiak
authors.affiliation: Department of Pharmacogenomics, Faculty of Pharmacy, Medical University, 02-097 Warszawa, Poland. marta.struga@wum.edu.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Struga
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D018441:Biofilms / Q000187:drug effects*; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013854:Thioamides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C000621027:1-(4-fluoro-3-chlorophenyl)-3-(1H-1,2,4-triazol-3-yl)thiourea; C000621028:5-amino-N-(prop-2-en-1-yl)-1H-1,2,4-triazole-1-carbothioamide; D000900:Anti-Bacterial Agents; D013854:Thioamides; D014230:Triazoles; D013890:Thiourea