Novel Meta-iodobenzylguanidine-Based Copper Thiosemicarbazide-1-guanidinomethylbenzyl Anticancer Compounds Targeting Norepinephrine Transporter in Neuroblastoma.

Meta-iodobenzylguanidine (MIBG) is a ligand with high affinity against norepinephrine transporter (NET) that has been used for diagnostic imaging and radionuclide therapy of NET-expressing tumors, such as neuroblastoma. We hypothesize that MIBG can be used as a ligand for development of new anticancer drugs targeting NET-expressing neuroblastoma (NB). To test our hypothesis, we synthesized two MIBG-based anticancer copper complexes [Cu(m-TSBG) and Cu(p-TSBG)] by conjugation of a thiosemicarbazone copper group onto MIBG ligand. Both Cu(m-TSBG) and Cu(p-TSBG) compounds showed potent anticancer activity against NB cells (BE2C and SK-N-DZ cells). The NB-specific anticancer activity of Cu(m-TSBG) and Cu(p-TSBG) was further demonstrated by the reduced anticancer activities when nonconjugated MIBG ligand was used to competitively block binding of Cu(m-TSBG) or Cu(p-TSBG) onto NET-expressing NB cells. Both Cu(m-TSBG) or Cu(p-TSBG) compounds hold potential as promising new drugs for targeted therapy of neuroblastoma and other NET-expressing tumors.