Zalaru Christina, Dumitrascu Florea, Draghici Constantin, Ferbinteanu Marilena, Tarcomnicu Isabela, Marinescu Maria, Moldovan Zenovia, Nitulescu George Mihai, Tatia Rodica, Popa Marcela
Department of Inorganic Chemistry, Organic, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Road, 030018 Bucharest, Romania.
"C.D. Nenitescu" Institute of Organic and Supramolecular Chemistry, Romanian Academy, 202 B Splaiul Independentei, 060023 Bucharest, Romania.
Antibiotics (Basel). 2024 Nov 22;13(12):1119. doi: 10.3390/antibiotics13121119.
New haloaminopyrazole derivatives differing in the number of pyrazole nuclei - and -, respectively, were synthesized and characterized by H-NMR, C-NMR, IR, UV-Vis, and elemental analysis. The single-crystal X-ray diffraction method was used to describe compounds and . When tested on normal NCTC fibroblasts in vitro, the newly synthesized derivatives were shown to be non-cytotoxic at a dosage of 25 μg/mL. Two compounds and showed a high degree of biocompatibility. From the two series of compounds tested on HEp-2 human cervical carcinoma cells, compound showed a more pronounced antiproliferative effect. Gram-positive strains of ATCC25923, ATCC29212, Gram-negative strains of ATCC27853, and strains of ATCC25922 were used to test the newly synthesized compounds antibacterial and antibiofilm properties. Among the studied pyrazole compounds, 2 compounds and with fluorine content on the phenyl ring and 4 compounds , , , and with chlorine content on the phenyl ring were noted, which proved to be the most active compared with the two reference drugs, metronidazole and nitrofurantoin. The six compounds showed a broad spectrum of action against all four tested bacterial strains, the most active being compound , with a chlorine atom in the "4" position of the phenyl nucleus and a MIC of 460 μg/mL. Compounds and showed the best antibiofilm activity against the bacterial strain ATCC25923, with an MBIC of 230 μg/mL.
分别合成了吡唑核数量不同的新型卤代氨基吡唑衍生物，并通过氢核磁共振（H-NMR）、碳核磁共振（C-NMR）、红外光谱（IR）、紫外可见光谱（UV-Vis）和元素分析对其进行了表征。采用单晶X射线衍射法对化合物 和 进行了描述。在体外对正常的NCTC成纤维细胞进行测试时，新合成的衍生物在25μg/mL的剂量下显示无细胞毒性。两种化合物 和 表现出高度的生物相容性。在对人宫颈癌细胞系HEp-2测试的两个系列化合物中，化合物 表现出更显著的抗增殖作用。使用ATCC25923、ATCC29212革兰氏阳性菌株，ATCC27853革兰氏阴性菌株以及ATCC25922菌株来测试新合成化合物的抗菌和抗生物膜特性。在所研究的吡唑化合物中，注意到有2种在苯环上含氟的化合物 和 以及4种在苯环上含氯的化合物 、 、 和 ，与两种参考药物甲硝唑和呋喃妥因相比，它们被证明是最具活性的。这六种化合物对所有四种测试细菌菌株均表现出广谱活性，最具活性的是化合物 ，其苯核“4”位有一个氯原子，最低抑菌浓度（MIC）为460μg/mL。化合物 和 对细菌菌株ATCC25923表现出最佳的抗生物膜活性，最低生物膜抑制浓度（MBIC）为230μg/mL。
