Journal
MOLECULES
Volume 27, Issue 15, Pages -Publisher
MDPI
DOI: 10.3390/molecules27154996
Keywords
[1; 2; 4]triazolo[1; 5-a]pyrimidine; indole; antiproliferative activities; ERK signaling pathway
Funding
- National Natural Science Foundation of China [U2004123]
- Henan Association of Science and Technology [2020HYTP056]
- Science and Technology Department of Henan Province [20202310144]
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In this study, a series of [1,2,4]triazolo[1,5-a]pyrimidine indole derivatives were designed and synthesized as anticancer agents. Compound H12 showed the most potent antiproliferative activities against MGC-803, HCT-116, and MCF-7 cells, and it inhibited the ERK signaling pathway, induced cell apoptosis, and regulated cell cycle-related proteins.
[1,2,4]Triazolo[1,5-a]pyrimidine and indole skeletons are widely used to design anticancer agents. Therefore, in this work, a series of [1,2,4]triazolo[1,5-a]pyrimidine indole derivatives were designed and synthesized by the molecular hybridization strategy. The antiproliferative activities of the target compounds H1-H18 against three human cancer cell lines, MGC-803, HCT-116 and MCF-7, were tested. Among them, compound H12 exhibited the most active antiproliferative activities against MGC-803, HCT-116 and MCF-7 cells, with IC50 values of 9.47, 9.58 and 13.1 mu M, respectively, which were more potent than that of the positive drug 5-Fu. In addition, compound H12 could dose-dependently inhibit the growth and colony formation of MGC-803 cells. Compound H12 exhibited significant inhibitory effects on the ERK signaling pathway, resulting in the decreased phosphorylation levels of ERK1/2, c-Raf, MEK1/2 and AKT. Furthermore, compound 12 induced cell apoptosis and G2/M phase arrest, and regulated cell cycle-related and apoptosis-related proteins in MGC-803 cells. Taken together, we report here that [1,2,4]triazolo[1,5-a]pyrimidine indole derivatives, used as anticancer agents via the suppression of ERK signaling pathway and the most active compound, H12, might be a valuable hit compound for the development of anticancer agents.
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