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

被引:14
作者
Roman, Roxana [1 ]
Pintilie, Lucia [2 ]
Caproiu, Miron Teodor [3 ]
Dumitrascu, Florea [3 ]
Nuta, Diana Camelia [1 ]
Zarafu, Irina [4 ]
Ionita, Petre [4 ]
Chifiriuc, Mariana Carmen [5 ,6 ,7 ]
Chirita, Cornel [8 ]
Morosan, Alina [9 ]
Popa, Marcela [5 ,6 ]
Bleotu, Coralia [5 ,6 ,10 ,11 ]
Limban, Carmen [1 ]
机构
[1] Carol Davila Univ Med & Pharm, Fac Pharm, Dept Pharmaceut Chem, 6 Traian Vuia, Bucharest 020956, Romania
[2] Natl Inst Chem Pharmaceut Res & Dev, 112 Vitan Ave, Bucharest 031299, Romania
[3] CD Nenitzescu Inst Organ & Supramol Chem, 202B Splaiul Independentei, Bucharest 060023, Romania
[4] Univ Bucharest, Fac Chem, Dept Organ Chem Biochem & Catalysis, 4-12 Regina Elisabeta, Bucharest 030018, Romania
[5] Univ Bucharest, Fac Biol, Dept Microbiol, Bucharest 060101, Romania
[6] Univ Bucharest, Res Inst Univ Bucharest ICUB, Bucharest 060101, Romania
[7] Romanian Acad, Bucharest 010071, Romania
[8] Carol Davila Univ Med, Fac Pharm, Dept Pharmacol & Clin Pharm, 6 Traian Vuia, Bucharest 020956, Romania
[9] Univ Politehn Bucuresti, Fac Appl Chem & Mat Sci, Dept Organ Chem Costin Nenitescu, Bucharest 011061, Romania
[10] Stefan S Nicolau Inst Virol, Dept Celular & Mol Pathol, 285 Mihai Bravu Ave, Bucharest 030304, Romania
[11] Acad Romanian Scientists, Ilfov 3, Bucharest 050044, Romania
来源
ANTIBIOTICS-BASEL | 2023年 / 12卷 / 05期
关键词
thiourea derivatives; benzamide; antimicrobial activity; antioxidant activity; synthesis; reversed phase HPLC; validation; ANTIBACTERIAL ACTIVITIES; STRUCTURAL-CHARACTERIZATION; ANTIMICROBIAL ACTIVITY; MOLECULAR DOCKING; CYTOTOXICITY; DESIGN; TOXICITY; MOIETY;
D O I
10.3390/antibiotics12050807
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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.
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页数:25
相关论文
共 79 条
[61]   Chemical and biological evaluation of some new antipyrine derivatives with particular properties [J].
Remes, C. ;
Paun, A. ;
Zarafu, I. ;
Tudose, M. ;
Caproiu, M. T. ;
Ionita, G. ;
Bleotu, C. ;
Matei, L. ;
Ionita, P. .
BIOORGANIC CHEMISTRY, 2012, 41-42 :6-12
[62]   A QSAR STUDY ON THIOUREA DERIVATIVES - NEW APPROACHES IN DRUG DEVELOPMENT [J].
Roman, Roxana ;
Pintilie, Lucia ;
Nuta, Diana ;
Limban, Carmen .
FARMACIA, 2022, 70 (02) :228-240
[63]  
Sadaphal P, 2022, International Journal of Pharmaceutical Sciences Review and Research, P23, DOI [10.47583/ijpsrr.2022.v74i02.003, 10.47583/ijpsrr.2022.v74i02.003, DOI 10.47583/IJPSRR.2022.V74I02.003]
[64]   1-(4,6-Dimethylpyrimidin-2-yl)-3-(3,5-dinitrobenzoyl)thiourea monohydrate [J].
Saeed, Sohail ;
Rashid, Naghmana ;
Wong, Wing-Tak ;
Hussain, Rizwan .
ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 2011, 67 :O1094-U144
[65]   Synthesis, spectroscopic characterization, mass spectrometry, and crystal structure of N-{[(4-bromophenyl)amino]carbonothioyl}benzamide [J].
Saeed, Sohail ;
Rashid, Naghmana ;
Bhatti, Moazzam Hussain ;
Jones, Peter G. .
TURKISH JOURNAL OF CHEMISTRY, 2010, 34 (05) :761-770
[66]   Synthesis, spectroscopic characterization, crystal structure and antifungal activity of thiourea derivatives containing a thiazole moiety [J].
Saeed, Sohail ;
Rashid, Naghmana ;
Jones, Peter G. ;
Hussain, Rizwan ;
Bhatti, Moazzam Hussain .
CENTRAL EUROPEAN JOURNAL OF CHEMISTRY, 2010, 8 (03) :550-558
[67]   Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents [J].
Saeed, Sohail ;
Rashid, Naghmana ;
Jones, Peter G. ;
Ali, Muhammad ;
Hussain, Rizwan .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (04) :1323-1331
[68]  
Shakeel A, 2016, Journal of Drug Design and Medicinal Chemistry, V2, P10, DOI [10.11648/j.jddmc.20160201.12, 10.11648/j.jddmc.20160201.12, DOI 10.11648/J.JDDMC.20160201.12]
[69]  
Shalas AF, 2016, International Journal of Pharmacy and Pharmaceutical Sciences, V8, P297
[70]   Antibiotics versus biofilm: an emerging battleground in microbial communities [J].
Sharma, Divakar ;
Misba, Lama ;
Khan, Asad U. .
ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL, 2019, 8 (1)