New N-acyl Thiourea Derivatives: Synthesis, Standardized Quantification Method and In Vitro Evaluation of Potential Biological Activities
Roxana Roman,
Lucia Pintilie,
Miron Teodor Căproiu,
Florea Dumitrașcu,
Diana Camelia Nuță,
Irina Zarafu,
Petre Ioniță,
Mariana Carmen Chifiriuc,
Cornel Chiriță,
Alina Moroșan,
Marcela Popa,
Coralia Bleotu,
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 for Chemical-Pharmaceutical Research & Development, 112 Vitan Av., 031299 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
Diana Camelia Nuță
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia, 020956 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
Mariana Carmen Chifiriuc
Department of Microbiology, Faculty of Biology & Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060101 Bucharest, Romania
Cornel Chiriță
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania
Alina Moroșan
Department of Organic Chemistry “Costin Nenitescu”, Faculty of Applied Chemistry and Materials Science, University POLITEHNICA of Bucharest, 011061 Bucharest, Romania
Marcela Popa
Department of Microbiology, Faculty of Biology & Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060101 Bucharest, Romania
Coralia Bleotu
Department of Microbiology, Faculty of Biology & Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060101 Bucharest, Romania
Carmen Limban
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania
New N-acyl thiourea derivatives with heterocyclic rings have been synthesized by first obtaining isothiocyanate, which further reacted with a heterocyclic amine, characterized by (FT-IR, NMR spectroscopy and FT-ICR) and tested for their in vitro antimicrobial, anti-biofilm and antioxidant activities to obtain a drug candidate in a lead-optimization process. From the tested compounds, those bearing benzothiazole (1b) and 6-methylpyridine (1d) moieties revealed anti-biofilm activity against E. coli ATCC 25922 at MBIC values of 625 µg/mL. Compound 1d exhibited the highest antioxidant capacity (~43%) in the in vitro assay using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Considering the in vitro results, the highest anti-biofilm and antioxidant activities were obtained for compound 1d. Therefore, a reversed-phase high-performance liquid chromatography (RP-HPLC) method has been optimized and validated for the quantitative determination of compound 1d. The detection and quantitation limits were 0.0174 μg/mL and 0.0521 μg/mL, respectively. The R2 correlation coefficient of the LOQ and linearity curves were greater than 0.99, over the concentration range of 0.05 μg/mL–40 μg/mL. The precision and accuracy of the analytical method were within 98–102%, confirming that the method is suitable for the quantitative determination of compound 1d in routine quality control analyses. Evaluating the results, the promising potential of the new N-acyl thiourea derivatives bearing 6-methylpyridine moiety will be further investigated for developing agents with anti-biofilm and antioxidant activities.
