title: Ternary copper(II)-polypyridyl enantiomers: aldol-type condensation, characterization, DNA-binding recognition, BSA-binding and anticancer property.
abstract: Chiral enantiomers [Cu(phen)(L-threo)(H2O)]NO3 1 and [Cu(phen)(D-threo)(H2O)]NO3 2 (threo = threoninate) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(II) complexes, viz. L- and D-[Cu(phen)(5MeOCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; 5MeOCA = 5-methyloxazolidine-4-carboxylate; x = 0-3) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-Visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. Analysis of restriction enzyme inhibition by these four complexes revealed modulation of DNA binding selectivity by the type of ligand, ligand modification and chirality. Their interaction with bovine serum albumin was investigated by FL and electronic spectroscopy. With the aid of the crystal structure of BSA, spectroscopic evidence suggested their binding at the cavity containing Trp134 with numerous Tyr residues in subdomain IA. The products were more antiproliferative than cisplatin against cancer cell lines HK-1, MCF-7, HCT116, HSC-2 and C666-1 except HL-60, and were selective towards nasopharyngeal cancer HK-1 cells over normal NP69 cells of the same organ type.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. NgChewHee@imu.edu.my
authors.forename: Chew-Hee
authors.initials: CH
authors.lastname: Ng
authors.forename: Wai-San
authors.initials: WS
authors.lastname: Wang
authors.forename: Kok-Vei
authors.initials: KV
authors.lastname: Chong
authors.forename: Yip-Foo
authors.initials: YF
authors.lastname: Win
authors.forename: Kian-Eang
authors.initials: KE
authors.lastname: Neo
authors.forename: Hong-Boon
authors.initials: HB
authors.lastname: Lee
authors.forename: Swee-Lan
authors.initials: SL
authors.lastname: San
authors.forename: Raja Noor Zaliha
authors.initials: RN
authors.lastname: Raja Abd Rahman
authors.forename: Weng Kee
authors.initials: WK
authors.lastname: Leong
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004854:Herpesvirus 4, Human; D006801:Humans; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012710:Serum Albumin, Bovine; D003300:Copper; D004247:DNA