Wang, Shuai published the artcileDiscovery of new [1,2,4] Triazolo[1,5-a]Pyrimidine derivatives that Kill gastric cancer cells via the mitochondria pathway, Synthetic Route of 24415-66-5, the main research area is triazolopyrimidinylamino diarylpropenone preparation antitumor activity SAR; 1,2,4]triazolo[1,5-a]pyrimidines; Apoptosis; Autophagy; Gastric cancer; Mitochondrial pathway.
A novel series of [1,2,4]triazolo[1,5-a]pyrimidine-based compoundsI [R1 = benzyl, 4-fluorobenzyl, 4-chlorobenzyl, etc.; R2 = Me, Et, Ph; R3 = H, Me] and II [R4 = Ph, (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl), (4-(3-(5-bromo-2-pyridyl)prop-2-enoyl)phenyl), etc.] were synthesized and tested their anti-proliferation efficacy against gastric cancer cell line MGC-803. Among them, compounds II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl), (4-(3-(5-bromo-2-pyridyl)prop-2-enoyl)phenyl)] inhibited gastric cancer cells at micromolar level. Compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] 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 II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] against gastric cancer cell. To our surprising, ROS level was increased by compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] 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 II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] in MGC-803 cells. Taken together, compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] exhibited its anti-proliferative activity via increasing ROS level and inducing autophagy, thus leading to apoptosis of gastric cancer cells. Therefore, compound II [R4 = (4-(3-(6-bromo-2-pyridyl)prop-2-enoyl)phenyl)] may support further development of lead compounds for gastric cancer therapy via mitochondria pathway.
European Journal of Medicinal Chemistry published new progress about Antitumor agents. 24415-66-5 belongs to class triazoles, name is 7-Chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine, and the molecular formula is C6H5ClN4, Synthetic Route of 24415-66-5.
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics