New N-acyl Thiourea Derivatives: Synthesis, Standardized Quantification Method and In Vitro Evaluation of Potential Biological Activities

New N-acyl thiourea derivatives with heterocyclic rings have been synthesized by first obtaining isothiocyanate, which further reacted with a heterocyclic amine, characterized by (FTIR, 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 antibiofilm activity against E. coli ATCC 25922 at MBIC values of 625 mu g/mL. Compound 1d exhibited the highest antioxidant capacity (similar to 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 mu g/mL and 0.0521 mu g/mL, respectively. The R-2 correlation coefficient of the LOQ and linearity curves were greater than 0.99, over the concentration range of 0.05 mu g/mL-40 mu g/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.

Automated summary

New N-acyl thiourea derivatives with heterocyclic rings were synthesized and characterized. In vitro tests showed antibiofilm and antioxidant activities for compound 1d. A RP-HPLC method was optimized for quantitative determination of compound 1d. The promising potential of these derivatives will be further investigated for drug development.