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

  • J Med Chem. 2019 Aug 8;62(15):6985-6991. doi: 10.1021/acs.jmedchem.9b00386.
Haiyuan Zhang  1 ,  Fang Xie  2 ,  Muhua Cheng  3 ,  Fangyu Peng  1  2  4
Affiliations
  • 1. Carman & Ann Adams Department of Pediatrics, School of Medicine , Wayne State University , Detroit , Michigan 48201 , United States.
  • 2. Department of Radiology , University of Texas Southwestern Medical Center , Dallas , Texas 735390 , United States.
  • 3. Department of Nuclear Medicine , Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , Guangdong 510630 , P. R. China.
  • 4. Harold C. Simmons Comprehensive Cancer Center , University of Texas Southwestern Medical Center , Dallas , Texas 75390 , United States.
PMID: 31283215 DOI: 10.1021/acs.jmedchem.9b00386
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.

Products