Design and synthesis of a siderophore conjugate as a potent PSMA inhibitor and potential diagnostic agent for prostate cancer.
A siderophore conjugate was designed as a potential PSMA inhibitor and diagnostic agent for prostate cancer. A semi-rigid spacer was incorporated to avoid competitive participation of iron binding by the enzyme inhibitor relative to the siderophore component. Biological test results showed that, even with the extended scaffold, this compound is a potent PSMA inhibitor with an IC50 of 4 nM. This siderophore conjugate may be useful for detection of prostate-derived cancer cells by magnetic resonance imaging (MRI).
Ding
Pingyu
P
Department of Chemistry and Biochemistry and Notre Dame Cancer Research Center, University of Notre Dame, Notre Dame, IN 46556, USA.
Helquist
Paul
P
Miller
Marvin J
MJ
D003432:Cross-Linking Reagents; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D008279:Magnetic Resonance Imaging; D008297:Male; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D017262:Siderophores / Q000737:chemistry* / Q000494:pharmacology
D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D017262:Siderophores; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen