title: Design an anticancer copper(II) pro-drug based on the flexible IIA subdomain of human serum albumin.
abstract: Owing to the flexible IIA sub-domain of human serum albumin (HSA), we proposed to rationally design a metal agent with a leaving group, and then regulate a leaving group of metal agent to be displaced by His-242 for improving its delivery efficiency and selectivity. To confirm our hypothesis, we synthesized a copper(II) compound derived from 2-amino-5-chlorophenol 2-hydroxybenzaldehyde Schiff-base, containing a leaving group [pyridine, PRD], namely Cu(L)(PRD). The HSA complex structure revealed that Cu(L)(PRD) binds to the hydrophobic cavity in HSA IIA sub-domain, His242 of HSA replaces the pyridine ligand in Cu compound, coordinating with Cu2+. HSA complex enhances cytotoxicity by about 1.4-fold in cancer cells but has no effect on normal cells in vitro through selectively accumulating into cancer cells. Interestingly, HSA complex has stronger anticancer capacity relative to unbound Cu(L)(PRD).
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Zhenlei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gou
authors.affiliation: Guangxi Universities Key Laboratory of Stem Cell and Pharmaceutical Biotechnology, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Hamid
authors.initials: H
authors.lastname: Khan
authors.affiliation: Guangxi Universities Key Laboratory of Stem Cell and Pharmaceutical Biotechnology, Guangxi Normal University, Guilin, Guangxi, China. Electronic address: zhouzuping@mailbox.gxnu.edu.cn.
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China. Electronic address: hliang@mailbox.gxnu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.affiliation: State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, Guangxi, China; Guangxi Universities Key Laboratory of Stem Cell and Pharmaceutical Biotechnology, Guangxi Normal University, Guilin, Guangxi, China. Electronic address: fyang@mailbox.gxnu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D008958:Models, Molecular; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D000072417:Protein Domains; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D011355:Prodrugs; D012709:Serum Albumin; D003300:Copper
keywords: Albumin; Apoptosis; Drug carrier; Pro-drug; Targeting