92193-33-4Relevant academic research and scientific papers
Diaryl-substituted thiosemicarbazone: A potent scaffold for the development of New Delhi metallo-β-lactamase-1 inhibitors
Li, Jia-Qi,Sun, Le-Yun,Jiang, Zhihui,Chen, Cheng,Gao, Han,Chigan, Jia-Zhu,Ding, Huan-Huan,Yang, Ke-Wu
, (2020/12/30)
The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has become an emerging public health threat. Inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. A potent scaffold, diaryl-substituted thiosemicarbazone, was constructed and assayed with metallo-β-lactamases (MβLs). The obtained twenty-six molecules specifically inhibited NDM-1 with IC50 0.038–34.7 μM range (except 1e, 2e, and 3d), and 1c is the most potent inhibitor (IC50 = 0.038 μM). The structure-activity relationship of synthetic thiosemicarbazones revealed that the diaryl-substitutes, specifically 2-pyridine and 2-hydroxylbenzene improved inhibitory activities of the inhibitors. The thiosemicarbazones exhibited synergistic antimycobacterial actions against E. coli-NDM-1, resulted a 2–512-fold reduction in MIC of meropenem, while 1c restored 16–256-, 16-, and 2-fold activity of the antibiotic on clinical isolates ECs, K. pneumonia and P. aeruginosa harboring NDM-1, respectively. Also, mice experiments showed that 1c had a synergistic antibacterial ability with meropenem, reduced the bacterial load clinical isolate EC08 in the spleen and liver. This work provided a highly promising scaffold for the development of NDM-1 inhibitors.
Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents
Bo-Wang,He, Zhang-Xu,Li, Yi-Han,Liu, Hong-Min,Ma, Li-Ying,Ma, Qin,Tao, Yuan-Yuan,Wang, Hao-Jie,Wu, Hui-Pan,Zhang, Xin-Hui,Zhao, Bing
, (2020/05/19)
In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial–mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer.
Synthesis, activity, and pharmacophore development for isatin-β- thiosemicarbazones with selective activity toward multidrug-resistant cells
Hall, Matthew D.,Salam, Noeris K.,Hellawell, Jennifer L.,Fales, Henry M.,Kensler, Caroline B.,Ludwig, Joseph A.,Szakács, Gergely,Hibbs, David E.,Gottesman, Michael M.
experimental part, p. 3191 - 3204 (2010/03/31)
We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-β- thiosemicarbazones from our initial stud
