3922-47-2Relevant articles and documents
Synthesis and fungicidal activity of phenazine-1-carboxylic triazole derivatives
Li, Xu-Jun,Zhang, Wei,Zhao, Chi-Na,Wu, Qing-Lai,Li, Jun-Kai,Xu, Zhi-Hong
, p. 452 - 465 (2021)
A total of 15 novel-substituted 3-(benzylsulfanyl)-1H-1,2,4-triazol-5-ylamine and 10 novel-substituted 3-benzylmercapto-1,2,4-triazol derivatives were synthesized based on the natural product phenazine-1-carboxylic acid (PCA). Their structures were confirmed by 1H-NMR, 13C-NMR, HRMS, and X-ray. Most substituted 3-benzylmercapto-1,2,4-triazol derivatives displayed very strong fungicidal activity against one or multiple plant pathogens in?vitro and in?vivo. Compounds 8b, 8h, and 8i showed a broad spectrum of fungicidal activity. Further field experiments indicated that compounds 8b, 8c, and 8h displayed better efficacy against rice blast (Pyricularia oryzae) than PCA. These data demonstrate that compounds 8b, 8c, and 8h are promising fungicidal candidates, deserving further studies. (Figure presented.).
Discovery of the Triazolo[1,5- a]Pyrimidine-Based Derivative WS-898 as a Highly Efficacious and Orally Bioavailable ABCB1 Inhibitor Capable of Overcoming Multidrug Resistance
Wang, Shuai,Wang, Sai-Qi,Teng, Qiu-Xu,Lei, Zi-Ning,Chen, Zhe-Sheng,Chen, Xiao-Bing,Liu, Hong-Min,Yu, Bin
, p. 16187 - 16204 (2021/11/18)
Targeting P-glycoprotein (ABCB1 or P-gp) has been recognized as a promising strategy to overcome multidrug resistance. Here, we reported our medicinal chemistry efforts that led to the discovery of the triazolo[1,5-a]pyrimidine derivative WS-898 as a highly effective ABCB1 inhibitor capable of reversing paclitaxel (PTX) resistance in drug-resistant SW620/Ad300, KB-C2, and HEK293/ABCB1 cells (IC50 = 5.0, 3.67, and 3.68 nM, respectively), more potent than verapamil and zosuquidar. WS-898 inhibited the efflux function of ABCB1, thus leading to decreased efflux and increased intracellular PTX concentration in SW620/Ad300 cells. The cellular thermal shift assay indicated direct engagement of WS-898 to ABCB1. Furthermore, WS-898 stimulated the ATPase activity of ABCB1 but had minimal effects on cytochrome P450 3A4 (CYP3A4). Importantly, WS-898 increased PTX sensitization in vivo without obvious toxicity. The results suggest that WS-898 is a highly effective triazolo[1,5-a]pyrimidine-based ABCB1 inhibitor and shows promise in reversing ABCB1-mediated PTX resistance.
Discovery of new [1,2,4] Triazolo[1,5-a]Pyrimidine derivatives that Kill gastric cancer cells via the mitochondria pathway
Wang, Shuai,Ma, Xu-Bin,Yuan, Xiao-Han,Yu, Bin,Xu, Yi-Chao,Liu, Hong-Min
, (2020/07/21)
Mitochondria are known as “powerhouse of cells” and play the role of a bridge in redox balance, cell apoptosis, and autophagy. ROS accumulation can cause mitochondria damage, while the injured mitochondria will further enhance ROS levels reciprocally. Herein, we synthesized a novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compounds 4a-4v and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds 4o and 4p inhibited gastric cancer cells at micromolar level. Compound 4o caused G2/M arrest and induced mitochondria-dependent apoptosis in MGC-803 and SGC-7901. However, inhibiting apoptosis pathway cannot prevent the inhibitory activity of compound 4o against gastric cancer cell. To our surprising, ROS level was increased by compound 4o and elevation of ROS could be rescued by NAC. In accordance with that, NAC absolutely prevented the anti-proliferation efficacy of compound 4o. We further found that autophagy inhibitor CQ rather than 3-MA partially reversed inhibitory activity of compound 4o in MGC-803 cells. Taken together, compound 4o exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound 4o may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.
