title: Developing Anticancer Ferric Prodrugs Based on the N-Donor Residues of Human Serum Albumin Carrier IIA Subdomain.
abstract: To improve the selectivity, delivery, and activity of ferric (Fe) anticancer agents, we design prodrugs based on N-donor residues of the human serum albumin (HSA) carrier IIA subdomain. We synthesized six Fe(III) compounds derived from 2-hydroxy-1-naphthaldehyde thiosemicarbazone (7-12). HSA complex structure revealed that Fe compound binds to the hydrophobic cavity in the HSA IIA subdomain. Lys199 and His242 of HSA replace the two Cl atoms of Fe compound, coordinating with Fe(3+). In vivo data revealed that compound 12 and HSA-12 complex inhibit the growth of the liver tumor and that the HSA-12 complex has stronger targeting ability and therapeutic efficacy than compound 12 alone. In addition, our results have shown that compound 12 and HSA-12 complex induce Bel-7402 cell death possible by several mechanisms.
authors.affiliation: School of Pharmacy, Nantong University , Nantong, Jiangsu 226019, China.
authors.forename: Jinxu
authors.initials: J
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Nantong University , Nantong, Jiangsu 226019, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gou
authors.affiliation: School of Pharmacy, Nantong University , Nantong, Jiangsu 226019, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nantong University , Nantong, Jiangsu 226019, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Nantong University , Nantong, Jiangsu 226019, China.
authors.forename: Shifang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Biology, Southern University of Science and Technology , Shenzhen, Guangdong 518055, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Ben May Department for Cancer Research, University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biology, Southern University of Science and Technology , Shenzhen, Guangdong 518055, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nantong University , Nantong, Jiangsu 226019, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nantong University , Nantong, Jiangsu 226019, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005290:Ferric Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D011355:Prodrugs; D012709:Serum Albumin