Contribution to the Synthesis, Characterization, Separation and Quantification of New <i>N</i>-Acyl Thiourea Derivatives with Antimicrobial and Antioxidant Potential
Roxana Roman,
Lucia Pintilie,
Diana Camelia Nuță,
Miron Teodor Căproiu,
Florea Dumitrașcu,
Irina Zarafu,
Petre Ioniță,
Ioana Cristina Marinaș,
Luminița Măruțescu,
Eleonora Kapronczai,
Simona Ardelean,
Carmen Limban
Affiliations
Roxana Roman
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania
Lucia Pintilie
National Institute of Chemical-Pharmaceutical Research & Development, 112 Vitan Av., 031299 Bucharest, Romania
Diana Camelia Nuță
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania
Miron Teodor Căproiu
“C. D. Nenitzescu” Institute of Organic and Supramolecular Chemistry, 202B Splaiul Independenței, 060023 Bucharest, Romania
Florea Dumitrașcu
“C. D. Nenitzescu” Institute of Organic and Supramolecular Chemistry, 202B Splaiul Independenței, 060023 Bucharest, Romania
Irina Zarafu
Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 4-12 Regina Elisabeta, 030018 Bucharest, Romania
Petre Ioniță
Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 4-12 Regina Elisabeta, 030018 Bucharest, Romania
Ioana Cristina Marinaș
Research Institute of the University of Bucharest, University of Bucharest, 90 Panduri Road, 030018 Bucharest, Romania
Luminița Măruțescu
Sanimed International Impex S.R.L., 087040 Calugareni, Romania
Eleonora Kapronczai
Supramolecular Organic and Organometallic Chemistry Centre, Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babeş-Bolyai University, 11 Arany János, 400028 Cluj-Napoca, Romania
Simona Ardelean
Department of Pharmaceutical Technology, Faculty of Pharmacy, “Vasile Goldiș” Western University, 86 Liviu Rebreanu, 310045 Arad, Romania
Carmen Limban
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania
The present study aimed to synthesize, characterize, and validate a separation and quantification method of new N-acyl thiourea derivatives (1a–1o), incorporating thiazole or pyridine nucleus in the same molecule and showing antimicrobial potential previously predicted in silico. The compounds have been physiochemically characterized by their melting points, IR, NMR and MS spectra. Among the tested compounds, 1a, 1g, 1h, and 1o were the most active against planktonic Staphylococcus aureus and Pseudomonas aeruginosa, as revealed by the minimal inhibitory concentration values, while 1e exhibited the best anti-biofilm activity against Escherichia coli (showing the lowest value of minimal inhibitory concentration of biofilm development). The total antioxidant activity (TAC) assessed by the DPPH method, evidenced the highest values for the compound 1i, followed by 1a. A routine quality control method for the separation of highly related compounds bearing a chlorine atom on the molecular backbone (1g, 1h, 1i, 1j, 1m, 1n) has been developed and validated by reversed-phase high-performance liquid chromatography (RP—HPLC), the results being satisfactory for all validation parameters recommended by the ICH guidelines (i.e., system suitability, specificity, the limits of detection and quantification, linearity, precision, accuracy and robustness) and recommending it for routine separation of these highly similar compounds.
