Janowski Michał, Janowska Sara, Andrzejczuk Sylwia, Kosikowska Urszula, Jasiński Radomir, Mirosław Barbara, Feldo Marcin, Wujec Monika, Demchuk Oleg M
Medical University of Lublin, Doctoral School, 7 Chodzki Str., 20-093 Lublin, Poland.
Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Biomedical Sciences, Medical University of Lublin, 1 Chodzki Str., 20-093 Lublin, Poland.
Molecules. 2025 Aug 11;30(16):3343. doi: 10.3390/molecules30163343.
The search for new antimicrobial agents is one of the major challenges in contemporary medicinal chemistry due to the global issue of increasing drug resistance. In our efforts to identify chemical structures with antibiotic activity that differ from commonly used antibiotics, we focused our research on (thio)semicarbazides and hydrazones. Guided by literature reports, we designed and synthesized a series of novel semicarbazides, thiosemicarbazides, and hydrazones based on the structure of 4-(morpholino-4-yl)-3-nitrobenzohydrazide. The obtained derivatives were subsequently evaluated in in vitro assays for their activity against reference strains of Gram-positive and Gram-negative bacteria. Among the studied groups of compounds, the semicarbazide derivatives exhibited the highest activity. The most active compound identified in the study was a semicarbazide containing a 4-bromophenyl moiety. This compound showed antibacterial potential against Enterococcus faecalis, with a MIC value of 3.91 µg/mL. Among the thiosemicarbazides, the most active compound contained a 4-trifluoromethylphenyl group, with MIC values against Gram-positive bacterial strains (excluding Staphylococcus aureus) ranging from 31.25 to 62.5 µg/mL. None of the tested hydrazones exhibited antimicrobial activity against the examined bacteria. Additionally, the structures of the new compounds were confirmed by single-crystal X-ray analysis, which enabled the investigation of their properties using advanced quantum chemical calculations.
由于耐药性不断增加这一全球性问题，寻找新型抗菌剂是当代药物化学面临的主要挑战之一。在我们努力确定具有不同于常用抗生素的抗生素活性的化学结构时，我们将研究重点放在了（硫）氨基脲和腙上。在文献报道的指导下，我们基于4-（吗啉-4-基）-3-硝基苯甲酰肼的结构设计并合成了一系列新型氨基脲、硫代氨基脲和腙。随后，对所获得的衍生物进行体外试验，评估它们对革兰氏阳性和革兰氏阴性细菌参考菌株的活性。在所研究的化合物组中，氨基脲衍生物表现出最高的活性。该研究中鉴定出的最具活性的化合物是一种含有4-溴苯基部分的氨基脲。该化合物对粪肠球菌显示出抗菌潜力，MIC值为3.91µg/mL。在硫代氨基脲中，最具活性的化合物含有一个4-三氟甲基苯基，对革兰氏阳性细菌菌株（不包括金黄色葡萄球菌）的MIC值范围为31.25至62.5µg/mL。所测试的腙均未对所检测的细菌表现出抗菌活性。此外，通过单晶X射线分析确认了新化合物的结构，这使得能够使用先进的量子化学计算来研究它们的性质。
