Roman Roxana, Pintilie Lucia, Nuță Diana Camelia, Căproiu Miron Teodor, Dumitrașcu Florea, Zarafu Irina, Ioniță Petre, Marinaș Ioana Cristina, Măruțescu Luminița, Kapronczai Eleonora, Ardelean Simona, Limban Carmen
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania.
National Institute of Chemical-Pharmaceutical Research & Development, 112 Vitan Av., 031299 Bucharest, Romania.
Pharmaceutics. 2023 Oct 20;15(10):2501. doi: 10.3390/pharmaceutics15102501.
The present study aimed to synthesize, characterize, and validate a separation and quantification method of new -acyl thiourea derivatives (-), 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, , , , and were the most active against planktonic and , as revealed by the minimal inhibitory concentration values, while exhibited the best anti-biofilm activity against (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 followed by . A routine quality control method for the separation of highly related compounds bearing a chlorine atom on the molecular backbone (, , , , , ) 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.
本研究旨在合成、表征并验证一种新的酰基硫脲衍生物(-)的分离和定量方法,该衍生物在同一分子中含有噻唑或吡啶核,且先前在计算机模拟中显示出抗菌潜力。这些化合物已通过熔点、红外光谱、核磁共振光谱和质谱进行了物理化学表征。通过最低抑菌浓度值可知,在所测试的化合物中,[具体化合物1]、[具体化合物2]、[具体化合物3]和[具体化合物4]对浮游菌[具体菌1]和[具体菌2]的活性最强,而[具体化合物5]对[具体菌3]表现出最佳的抗生物膜活性(生物膜形成的最低抑菌浓度值最低)。通过DPPH法评估的总抗氧化活性(TAC)表明,化合物[具体化合物6]的值最高,其次是[具体化合物7]。已开发并通过反相高效液相色谱(RP-HPLC)验证了一种用于分离分子主链上带有氯原子的高度相关化合物([具体化合物8]、[具体化合物9]、[具体化合物10]、[具体化合物11]、[具体化合物12]、[具体化合物13])的常规质量控制方法,结果对于ICH指南推荐的所有验证参数(即系统适用性、特异性、检测限和定量限、线性、精密度、准确度和稳健性)均令人满意,并推荐将其用于这些高度相似化合物的常规分离。