Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor.

Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer's disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated.

Macrocyclic polyamines deplete cellular ATP levels and inhibit cell growth in human prostate cancer cells.

In solid tumors, when O(2) partial pressure drops below 10 mmHg, ATP levels rapidly decrease due to the Warburg effect. It is known that certain macrocyclic polyamines catalyze the chemical hydrolysis of ATP with release of inorganic phosphate. Since tumor cells have diminished ATP levels as compared to normal cells, we attempted to deplete cellular ATP with macrocyclic polyamines in an effort to inhibit tumor cell proliferation.