59565-50-3Relevant academic research and scientific papers
Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway
Xiao, Shengnan,Wang, Xude,Xu, Lei,Li, Tao,Cao, Jiaqing,Zhao, Yuqing
, (2020/07/23)
In this study, we introduced 1, 2, 4-triazole groups into panaxadiol (PD) to obtain 18 panaxadiol triazole derivatives. Five cancer cells and one normal cell were evaluated for cytotoxicity by MTT assay. The results showed that most of the derivatives could inhibit cancer cell proliferation, and the anti-proliferative activity of compound A1 was the most significant. For HepG-2 cells, the IC50 value was 4.21 ± 0.54 μM, which was nearly 15 times higher than the activity of PD. Further studies showed that compound A1 could induce apoptosis in HepG-2 cells, and could enhance the expression of Cl-caspase-3, Cl-caspase-9 and Cl-PARP. Moreover, Western blot analysis showed that after treating HepG-2 cells with compound A1, the expression of p53 protein was increased and the ratio of Bax/Bcl-2 was gradually increased. The cytoplasmic Bax is then translocated to the mitochondria, causing the release of Cyt c protein. Therefore, the results indicate that compound A1 induces apoptosis through the mitochondrial pathway and can be used the potential to develop new anti-proliferative agents.
Design, Synthesis and Evaluation of Triazole-Pyrimidine Analogues as SecA Inhibitors
Cui, Jianmei,Jin, Jinshan,Chaudhary, Arpana Sagwal,Hsieh, Ying-Hsin,Zhang, Hao,Dai, Chaofeng,Damera, Krishna,Chen, Weixuan,Tai, Phang C.,Wang, Binghe
, p. 43 - 56 (2016/01/15)
SecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. Through a combination of virtual screening and experimental exploration of the surrounding chemical space, we identified a hit bistriazole SecA inhibitor, SCA-21, and studied a series of analogues by systematic dissections of the core scaffold. Evaluation of these analogues allowed us to establish an initial structure-activity relationship in SecA inhibition. The best compounds in this group are potent inhibitors of SecA-dependent protein-conducting channel activity and protein translocation activity at low- to sub-micromolar concentrations. They also have minimal inhibitory concentration (MIC) values against various strains of bacteria that correlate well with the SecA and protein translocation inhibition data. These compounds are effective against methicillin-resistant Staphylococcus aureus strains with various levels of efflux pump activity, indicating the capacity of SecA inhibitors to null the effect of multidrug resistance. Results from studies of drug-affinity-responsive target stability and protein pull-down assays are consistent with SecA as a target for these compounds. One stone, several birds! The SecA inhibitors discovered in this study are broad-spectrum antimicrobials with the intrinsic ability to null the effect of efflux pumps. They are therefore effective against multidrug-resistant bacterial strains, can inhibit virulence factor secretion, and are very active against strains of bacteria that are resistant to antibiotics in current use, including vancomycin.
Discovery of thiadiazole amides as potent, S1P3-sparing agonists of sphingosine-1-phosphate 1 (S1P1) receptor
Xu, Heng,Zhang, Haibo,Luan, Linbo,Xu, Yan,Li, Chengyong,Wang, Yonghui,Han, Fangbin,Yang, Ting,Ren, Feng,Xiang, Jia-Ning,Elliott, John D.,Zhao, Yonggang,Guo, Taylor B.,Lu, Hongtao,Zhang, Wei,Hirst, David,Lindon, Matthew,Lin, Xichen
scheme or table, p. 2456 - 2459 (2012/05/05)
High-throughput screening of GSK compound collection led to the discovery of a novel series of thiadiazole amides as potent and S1P3-sparing sphingosine-1-phosphate 1 (S1P1) receptor agonists. Synthesis, structure and activity relationship, selectivity, and some developability properties are described.
Fluorine containing heterocyclic compounds: Synthesis of 6-substituted-2-substituted-aryl-1,2,4-triazolo[5,1-b] 1,3,5-thiadiazin-7-one derivatives
Liu, Suyou,Qian, Xuhong,Song, Gonghua,Chen, Jing,Chen, Weidong
, p. 111 - 115 (2007/10/03)
A group of heterocylic compounds of condensed triazole-thiadiazinone derivatives containing fluorine (IIIa-h) were obtained in good yields by the reactions of the corresponding 3-aryl-5-mercapto-1,2,4-triazole (IIa-d) with N-substituted-N-chloromethyl carbamoyl chloride (I) in the presence of potassium carbonate in N,N-dimethylformamide at room temperature. Cyclization of 3-(2,3,5-trifluoro-4-methoxyl)phenyl-5-mercapto-1,2,4-triazole (IIe) with I was difficult due to an intermolecular hydrogen bond of IIe. The structures of the compounds synthesized were confirmed by IR, MS, 1H NMR and elemental analyses. Fungicidal and insecticidal activities of these compounds were also studied.
