title: Synthesis, hydrolytic DNA-cleaving activities and cytotoxicities of EDTA analogue-tethered pyrrole-polyamide dimer-based Ce(IV) complexes.
abstract: Two EDTA analogue-tethered C2-symmetrical dimeric monopyrrole-polyamide 5 and dipyrrole-polyamide 6, and their corresponding Ce(IV) complexes Ce-5 and Ce-6 were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicate that complexes Ce-5 and Ce-6 exhibited potent DNA-cleaving activities under physiological conditions. The maximal first-order rate constants (kmax's) were (0.42 ± 0.02) h(-1) for Ce-5 and (0.52 ± 0.02) h(-1) for Ce-6, respectively, suggesting that both complexes catalyzed the cleavage of supercoiled DNA by up to approximately 10(8)-fold. Complex Ce-6 exhibited ca 10-fold higher overall catalytic activity (kmax/KM) than Ce-5, which may be ascribed to its higher DNA-binding affinity. Inhibition experiments and a model study convincingly suggest that both complexes Ce-5 and Ce-6 functioned as hydrolytic DNA-cleavers. In addition, both complexes were found to display moderate inhibitory activity toward A549 and HepG-2 cells.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: huagongzhoucq@163.com.
authors.forename: Chun-Qiong
authors.initials: CQ
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: whchen@smu.edu.cn.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002563:Cerium / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry; D053837:DNA Cleavage / Q000187:drug effects*; D004278:DNA, Superhelical / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004492:Edetic Acid / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009757:Nylons / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004278:DNA, Superhelical; D009757:Nylons; D009942:Organometallic Compounds; D011758:Pyrroles; D002563:Cerium; D004492:Edetic Acid
keywords: Ce(IV) complex; Cytotoxicity; EDTA analogue; Hydrolytic DNA cleavage; Pyrrole-polyamide dimer