Cvijetić Ilija N, Herlah Barbara, Marinković Aleksandar, Perdih Andrej, Bjelogrlić Snežana K
Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
National Institute of Chemistry, Hajdrihova 19, SI 1000 Ljubljana, Slovenia.
Pharmaceuticals (Basel). 2023 Feb 23;16(3):341. doi: 10.3390/ph16030341.
Phenotypic screening of α-substituted thiocarbohydrazones revealed promising activity of 1,5-bis(salicylidene)thiocarbohydrazide against leukemia and breast cancer cells. Supplementary cell-based studies indicated an impairment of DNA replication via the ROS-independent pathway. The structural similarity of α-substituted thiocarbohydrazone to previously published thiosemicarbazone catalytic inhibitors targeting the ATP-binding site of human DNA topoisomerase IIα prompted us to investigate the inhibition activity on this target. Thiocarbohydrazone acted as a catalytic inhibitor and did not intercalate the DNA molecule, which validated their engagement with this cancer target. A comprehensive computational assessment of molecular recognition for a selected thiosemicarbazone and thiocarbohydrazone provided useful information for further optimization of this discovered lead compound for chemotherapeutic anticancer drug discovery.
对α-取代硫代碳腙的表型筛选显示，1,5-双（水杨醛）硫代碳酰肼对白血病和乳腺癌细胞具有有前景的活性。基于细胞的补充研究表明，其通过不依赖活性氧的途径损害DNA复制。α-取代硫代碳腙与先前发表的靶向人DNA拓扑异构酶IIα的ATP结合位点的硫代氨基脲催化抑制剂的结构相似性促使我们研究其对该靶点的抑制活性。硫代碳腙作为一种催化抑制剂，不插入DNA分子，这证实了它们与该癌症靶点的结合。对选定的硫代氨基脲和硫代碳腙进行的分子识别综合计算评估为进一步优化这种发现的先导化合物以用于化疗抗癌药物发现提供了有用信息。
