Department of Organic Chemistry, Medical University of Gdańsk, Gdańsk, Poland.
Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, Warsaw, Poland.
Eur J Med Chem. 2020 Mar 15;190:112106. doi: 10.1016/j.ejmech.2020.112106. Epub 2020 Jan 31.
The series of new 4-substituted picolinohydrazonamides were synthesized (6-25) and evaluated for tuberculostatic activity. Compounds having a hydrophilic cyclic amine such as morpholine and pyrrolidine at the end of the thiosemicarbazide chain, exhibited the highest antimycobacterial activity. The antimycobacterial activity of compounds 6, 11, and 15 (MIC 0.4-0.8 μg/mL) was higher than that of reference drugs. Moreover, derivative 15 exhibited lower activity against other tested microorganism such as bacteria gram-positive, gram-negative or fungi. Thus, this compound is characterized by the selectivity of antimicrobial activity. Antiproliferative study conducted against human dermal fibroblasts (HDF) and mouse melanoma cell line (B16-F10) revealed low cytotoxicity of compound 15. Conducted research allowed to identify compound 15 as leading for further research.
一系列新的 4-取代吡啶甲酰肼被合成（6-25）并评估其抗结核活性。在硫代缩氨基脲链末端具有亲水性环状胺（如吗啉和吡咯烷）的化合物表现出最高的抗分枝杆菌活性。化合物 6、11 和 15 的抗分枝杆菌活性（MIC 0.4-0.8μg/mL）高于参考药物。此外，衍生物 15 对其他测试的微生物如革兰氏阳性菌、革兰氏阴性菌或真菌的活性较低。因此，该化合物的特点是抗菌活性的选择性。对人皮肤成纤维细胞（HDF）和小鼠黑色素瘤细胞系（B16-F10）的抗增殖研究表明，化合物 15 的细胞毒性较低。进行的研究确定了化合物 15 作为进一步研究的先导化合物。
