59565-49-0Relevant academic research and scientific papers
Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction
Zhou, Wenjuan,Xu, Chenhao,Dong, Guanjun,Qiao, Hui,Yang, Jing,Liu, Hongmin,Ding, Lina,Sun, Kai,Zhao, Wen
, (2021/03/24)
Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.
Synthesis of 1,3,4-oxadiazoles as selective T-type calcium channel inhibitors
Zhang, Man,Zou, Bende,Gunaratna, Medha J.,Weerasekara, Sahani,Tong, Zongbo,Nguyen, Thi D.T.,Koldas, Serkan,Cao, William S.,Pascual, Conrado,Xie, Xinmin Simon,Hua, Duy H.
, p. 145 - 164 (2020/02/04)
– Neuropathic pain, epilepsy, insomnia, and tremor disorder may arrive from an increase of intracellular Ca2+ concentration through a dysfunction of T-type Ca2+ channels. Thus, T-type calcium channels could be a target in drug discovery for the treatments of neuropathic pain and epilepsy. From rational drug design approach, a group of 2,5-disubstituted 1,3,4-oxadiazole molecules was synthesized and their selective T-type channel inhibitions were evaluated. The synthetic strategy consists of a short sequence of three reactions: (i) condensation of thiosemicarbazide with acid chlorides; (ii) ring closing by 1,3-dibromo-5,5-dimethylhydantoin; and (iii) coupling with various acid chlorides. 5-Chloro-N-(5-phenyl-1,3,4-oxadiazol-2-yl)thiophene-2-carboxamide (11) was found to selectively inhibit T-type Ca2+ channel over Na+ and K+ channels in mouse dorsal root ganglion neurons and/or human embryonic kidney (HEK)-293 cells and to suppress seizure-induced death in mouse model. Consequently, compound 11 is a useful probe for investigation of physiologic and pathophysiologic roles of the T-channel, and provides a basis to develop a novel therapeutic to treat chronic neuropathic and inflammatory pains.
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.
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.
