Synthesis and antitumor activities of novel 3-(6-aminopyridin-3-yl)benzamide derivatives: Inducing cell cycle arrest and apoptosis via AURKB transcription inhibition.
Bioorg Chem
; 148: 107450, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38761704
ABSTRACT
Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC50 value of 0.04 ± 0.01 µM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzamides
/
Drug Screening Assays, Antitumor
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Apoptosis
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Cell Proliferation
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Dose-Response Relationship, Drug
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Cell Cycle Checkpoints
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Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Chem
Year:
2024
Document type:
Article
Affiliation country:
China