Paprocka Renata, Przybysz Monika, Pośpieszyńska Kamila, Chepkoech Ashley, Jagleniec Dominika, Godlewski Antoni, Korczak Karolina, Wiese-Szadkowska Małgorzata, Kutkowska Jolanta
Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Jurasza Str. 2, 85-089 Bydgoszcz, Poland.
Department of Pharmacy, Faculty of Health Sciences, University of Nairobi, KNH, Nairobi P.O. Box 2149-00202, Kenya.
Med Chem. 2025 Jul 15. doi: 10.2174/0115734064396576250706091217.
Bacterial diseases pose a significant challenge to modern medicine due to the rapid development of resistance by bacterial strains and the global migration of people, which facilitates the transmission of these diseases. Therefore, there is a need to develop new strategies to combat microorganisms and newer substances that could be used as antibiotics.
Six new derivatives, , containing a 4-oxybut-2-enoic acid moiety, were obtained by reacting amidrazones with maleic anhydride. The antimicrobial potency of compounds was studied using the microdilution method against the following bacterial strains: , and the fungal strain . Their antiproliferative activity was tested in cultures of human peripheral blood mononuclear cells stimulated with phytohemagglutinin. The bioavailability parameters of new compounds were predicted using Molinspiration software.
Derivatives showed the strongest antibacterial activity, especially against and . Compounds inhibited the growth of . Compounds exhibited low antiproliferative activity towards human peripheral blood mononuclear cells. However, it is necessary to evaluate whether all compounds are well absorbed after oral administration.
The most promising antibacterial activity was demonstrated by derivatives possessing a 2-pyridyl substituent at the R1 position () or a phenyl ring at the R position (2a, 2f).
Compound demonstrated the highest antibacterial activity and selectivity in inhibiting the growth of . Additionally, it exhibited low toxicity to human lymphocytes and demonstrated favorable bioavailability parameters. Therefore, its structure can be used as a starting point for designing new antimicrobials, such as targeted therapies for yersiniosis, beyond traditional antibiotics.
由于细菌菌株耐药性的快速发展以及人员的全球流动促进了这些疾病的传播，细菌性疾病对现代医学构成了重大挑战。因此，需要开发对抗微生物的新策略以及可作为抗生素使用的新型物质。
通过脒腙与马来酸酐反应获得了六种含有4-氧代丁-2-烯酸部分的新衍生物。使用微量稀释法研究了化合物对以下细菌菌株：以及真菌菌株的抗菌效力。在植物血凝素刺激的人外周血单核细胞培养物中测试了它们的抗增殖活性。使用Molinspiration软件预测了新化合物的生物利用度参数。
衍生物显示出最强的抗菌活性，尤其是对和。化合物抑制了的生长。化合物对人外周血单核细胞表现出低抗增殖活性。然而，有必要评估所有化合物口服后是否能被良好吸收。
在R1位置具有2-吡啶基取代基（）或在R位置具有苯环（2a，2f）的衍生物表现出最有前景的抗菌活性。
化合物在抑制的生长方面表现出最高的抗菌活性和选择性。此外，它对人淋巴细胞表现出低毒性，并显示出良好的生物利用度参数。因此，其结构可作为设计新型抗菌剂的起点，例如针对耶尔森氏菌病的靶向治疗，超越传统抗生素。
