title: Highly selective anti-cancer properties of ester functionalized enantiopure dinuclear gold(I)-diphosphine.
abstract: Two chiral (-)-diphosphine-digold(I) complexes containing mono- and di-methylester substituted diphosphine ligands have been prepared and structurally characterized. Both complexes are highly potent against breast cancer cell line MDA-MB-231 but showed much lower cytotoxicity against the normal human breast epithelial cells MCF10A. When compared with its mono-substituted analogue, the di-methylester substituted complex caused markedly lower and relatively insignificant damage to the normal breast cells. The analogous mono- and di-ethylester substituted complexes with the same stereochemistry exhibited similar anti-cancer properties but with noticeably higher cytotoxicity against the MCF10A cells. The enantiomeric complex (+)-diphosphine-digold(I) complexes containing the di-methylester substituted diphosphine ligand exhibited clearly different biological properties from its (-)-enantiomer. Furthermore, a structurally similar diphosphine-digold(I) complex but in the absence of an ester substituent, killed both the cancerous and the healthy cells indiscriminately. The current study thus revealed that the introduction of multi-esters, particularly methylesters, is an efficient approach to suppress the side-effects and to improve the efficiency of potential gold-based anti-cancer reagents. When combined with the biological observations, the chirality of gold complexes may serve as a sensitive probe for the future mechanistic studies.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Li
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Jia
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637616, Singapore.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Zhu
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Renta Jonathan
authors.initials: RJ
authors.lastname: Chew
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637616, Singapore; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, A*STAR, Singapore 138673, Singapore. Electronic address: nstan@ntu.edu.sg.
authors.forename: Nguan Soon
authors.initials: NS
authors.lastname: Tan
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore. Electronic address: pakhing@ntu.edu.sg.
authors.forename: Pak-Hing
authors.initials: PH
authors.lastname: Leung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry*; D006801:Humans; D010720:Phosphines / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D010720:Phosphines; D006046:Gold; C044646:phosphine
keywords: Breast cancer; Chirality; Ester–ester functionality; Phosphine gold drug