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

Haiyuan Zhang, Fang Xie, Muhua Cheng, Fangyu Peng

Research output: Contribution to journalArticle

Abstract

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)2 and Cu(p-TSBG)2] by conjugation of a thiosemicarbazone copper group onto MIBG ligand. Both Cu(m-TSBG)2 and Cu(p-TSBG)2 compounds showed potent anticancer activity against NB cells (BE2C and SK-N-DZ cells). The NB-specific anticancer activity of Cu(m-TSBG)2 and Cu(p-TSBG)2 was further demonstrated by the reduced anticancer activities when nonconjugated MIBG ligand was used to competitively block binding of Cu(m-TSBG)2 or Cu(p-TSBG)2 onto NET-expressing NB cells. Both Cu(m-TSBG)2 or Cu(p-TSBG)2 compounds hold potential as promising new drugs for targeted therapy of neuroblastoma and other NET-expressing tumors.

Original languageEnglish (US)
Pages (from-to)6985-6991
Number of pages7
JournalJournal of Medicinal Chemistry
Volume62
Issue number15
DOIs
StatePublished - Aug 8 2019

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Norepinephrine Plasma Membrane Transport Proteins
3-Iodobenzylguanidine
Neuroblastoma
Copper
Ligands
Thiosemicarbazones
Diagnostic Imaging
Drug Delivery Systems
Radioisotopes
thiosemicarbazide
Neoplasms
Drug Therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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Novel Meta-iodobenzylguanidine-Based Copper Thiosemicarbazide-1-guanidinomethylbenzyl Anticancer Compounds Targeting Norepinephrine Transporter in Neuroblastoma. / Zhang, Haiyuan; Xie, Fang; Cheng, Muhua; Peng, Fangyu.

In: Journal of Medicinal Chemistry, Vol. 62, No. 15, 08.08.2019, p. 6985-6991.

Research output: Contribution to journalArticle

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abstract = "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)2 and Cu(p-TSBG)2] by conjugation of a thiosemicarbazone copper group onto MIBG ligand. Both Cu(m-TSBG)2 and Cu(p-TSBG)2 compounds showed potent anticancer activity against NB cells (BE2C and SK-N-DZ cells). The NB-specific anticancer activity of Cu(m-TSBG)2 and Cu(p-TSBG)2 was further demonstrated by the reduced anticancer activities when nonconjugated MIBG ligand was used to competitively block binding of Cu(m-TSBG)2 or Cu(p-TSBG)2 onto NET-expressing NB cells. Both Cu(m-TSBG)2 or Cu(p-TSBG)2 compounds hold potential as promising new drugs for targeted therapy of neuroblastoma and other NET-expressing tumors.",
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AB - 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)2 and Cu(p-TSBG)2] by conjugation of a thiosemicarbazone copper group onto MIBG ligand. Both Cu(m-TSBG)2 and Cu(p-TSBG)2 compounds showed potent anticancer activity against NB cells (BE2C and SK-N-DZ cells). The NB-specific anticancer activity of Cu(m-TSBG)2 and Cu(p-TSBG)2 was further demonstrated by the reduced anticancer activities when nonconjugated MIBG ligand was used to competitively block binding of Cu(m-TSBG)2 or Cu(p-TSBG)2 onto NET-expressing NB cells. Both Cu(m-TSBG)2 or Cu(p-TSBG)2 compounds hold potential as promising new drugs for targeted therapy of neuroblastoma and other NET-expressing tumors.

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