Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent.
Bioorg Chem
; 143: 107094, 2024 Feb.
Article
in En
| MEDLINE
| ID: mdl-38199139
ABSTRACT
Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tubulin
/
Tubulin Modulators
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Chem
Year:
2024
Document type:
Article
Affiliation country:
Pakistan
Country of publication:
United States