1447697-54-2

Upstream product

• 86-74-8 9H-carbazole 
• 86-28-2 N-ethylcarbazole 
• 874-60-2 4-methyl-benzoyl chloride 

Relevant academic research and scientific papers

Modified carbazoles destabilize microtubules and kill glioblastoma multiform cells

Small molecules that target microtubules (MTs) represent promising therapeutics to treat certain types of cancer, including glioblastoma multiform (GBM). We synthesized modified carbazoles and evaluated their antitumor activity in GBM cells in culture. Modified carbazoles with an ethyl moiety linked to the nitrogen of the carbazole and a carbonyl moiety linked to distinct biaromatic rings exhibited remarkably different killing activities in human GBM cell lines and patient-derived GBM cells, with IC50 values from 67 to >10,000 nM. Measures of the activity of modified carbazoles with tubulin and microtubules coupled to molecular docking studies show that these compounds bind to the colchicine site of tubulin in a unique low interaction space that inhibits tubulin assembly. The modified carbazoles reported here represent novel chemical tools to better understand how small molecules disrupt MT functions and kill devastating cancers such as GBM.

MODIFIED CARBAZOLES AS THERAPEUTIC AGENTS

This disclosure relates to compounds that target microtubules, pharmaceutical compositions comprising them, and methods of using the compounds and compositions for treating diseases. More particularly, this disclosure relates to modified carbazole compounds and pharmaceutical compositions thereof, methods of targeting microtubules with these compounds, and methods of treating diseases affected by microtubule disruption.

COMPOSITIONS AND METHODS FOR TREATING MALIGNANT ASTROCYTOMAS

The disclosure provides methods of treating glioblastoma, methods of screening for compounds that treat glioblastoma, and pharmaceutical compositions useful in the treatment of glioblastoma.