Design, Synthesis, and Antitumor Activity of a Series of Novel 4-(Aromatic Sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-ones.
Naiguo XingChen ChenQiu ZhongShilong ZhengGuangdi WangLing HePublished in: Molecules (Basel, Switzerland) (2020)
Many sulfonamides show anticancer activity. Based on benzenesulfonylazaspirodienone (HL-X9) identified in our previous work, we optimized the lead compound for better efficacy, thereby synthesizing a series of novel 4-(aromatic sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-one derivatives through a key step of metal-catalyzed cascade cyclization. The preliminary antiproliferative tests have shown that the anticancer activities of acetyl-protected mannose-linked sulfonylazaspirodienone derivatives (7i-7l) have been greatly improved. Among them, 7j is the most potent derivative, with IC50 values of 0.17 µM, 0.05 µM, and 0.07 µM for A549, MDA-MB-231, and HeLa cell lines, respectively. Flow cytometry analysis shows that 7j arrests MDA-MB-231 cells in the G2/M phase and has a certain effect on the apoptosis of MDA-MB-231 cells. In addition, the acute toxicity of 7j was lower than that of adriamycin.
Keyphrases
- cell cycle arrest
- cell death
- pi k akt
- flow cytometry
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- breast cancer cells
- liver failure
- amino acid
- cardiac arrest
- escherichia coli
- respiratory failure
- mass spectrometry
- room temperature
- cystic fibrosis
- hepatitis b virus
- cardiopulmonary resuscitation
- ionic liquid
- pseudomonas aeruginosa
- mechanical ventilation
- drug induced
- aortic dissection