Antimicrobial and Anti-biofilm Activity of Thiourea Derivatives Bearing 3-amino-1H-1,2,4-triazole Scaffold

作者：Stefanska Joanna; Stepien Karolina; Bielenica Anna; Szulczyk Daniel; Miroslaw Barbara; Koziol Anna E; Sanna Giuseppina; Iuliano Filippo; Madeddu Silvia; Jozwiak Michal; Struga Marta^*

来源：Medicinal Chemistry, 2016, 12(5): 478-488.

DOI：10.2174/1573406412666151204003146

• Antimicrobial activity
• 3-amino-1H-1,2,4-triazole
• biofilm
• cytotoxicity
• thiourea derivatives

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 a 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 Csp(2) 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 mu g/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 mu g/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 mu g/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 mu M).

• 出版日期2016