title: Synthesis, characterization, and biological evaluation of new tetrazole-based platinum(II) and palladium(II) chlorido complexes--potent cisplatin analogues and their trans isomers.
abstract: Two series of tetrazole-containing platinum(II) and palladium(II) chlorido complexes, trans-[ML(2)Cl(2)] (M=Pt, Pd) and cis-[PtL(2)Cl(2)]·nH(2)O (n=0, 1), where L is 1- or 2-substituted 5-aminotetrazole, have been synthesized and thoroughly characterized. Configuration of platinum(II) complexes obtained from the reaction of 5-aminotetrazoles with K(2)PtCl(4) has been found to vary depending on the nature of tetrazole derivatives and reaction conditions. According to in vitro cytotoxic evaluation, only platinum complexes display noticeable antiproliferative effect, and their cytotoxicity depends strongly on their geometry and hydrophobicity of the carrier ligands. The most promising complexes are cis-[Pt(1-apt)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O, where 1-apt is 5-amino-1-phenyltetrazole and 2-abt is 5-amino-2-tert-butyltetrazole. In comparison with cisplatin, they show comparable cytotoxic potency against cisplatin-sensitive human cancer cell lines, cis-[Pt(2-abt)(2)Cl(2)]·H(2)O performing substantially higher activity against cisplatin-resistant cell lines. Cell cycle studies in H1299 cell line indicated that cis-[Pt(2-abt)(2)Cl(2)]·H(2)O induced apoptosis launched from G2 accumulations. The DNA interaction with cis-[Pt(1-apt)(2)Cl(2)]·H(2)O was followed by UV spectroscopy, circular dichroism, hydrodynamic and electrophoretic mobility studies. Both cis-[Pt(1-apt)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O complexes appeared to be significantly less toxic than cisplatin in mice, while only compound cis-[Pt(1-apt)(2)Cl(2)]·H(2)O displayed noticeable efficacy in vivo.
authors.affiliation: Research Institute for Physical Chemical Problems, Belarusian State University, Leningradskaya 14, 220030, Minsk, Belarus. serebryanskaya.t@gmail.com
authors.forename: Tatiyana V
authors.initials: TV
authors.lastname: Serebryanskaya
authors.forename: Tatiana
authors.initials: T
authors.lastname: Yung
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Bogdanov
authors.forename: Andrei
authors.initials: A
authors.lastname: Shchebet
authors.forename: Steven A
authors.initials: SA
authors.lastname: Johnsen
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Lyakhov
authors.forename: Ludmila S
authors.initials: LS
authors.lastname: Ivashkevich
authors.forename: Zhanna A
authors.initials: ZA
authors.lastname: Ibrahimava
authors.forename: Tatiyana S
authors.initials: TS
authors.lastname: Garbuzenco
authors.forename: Tatiyana S
authors.initials: TS
authors.lastname: Kolesnikova
authors.forename: Natalya I
authors.initials: NI
authors.lastname: Melnova
authors.forename: Pavel N
authors.initials: PN
authors.lastname: Gaponik
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Ivashkevich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002942:Circular Dichroism; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D007536:Isomerism; D008297:Male; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013777:Tetrazoles / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D009944:Organoplatinum Compounds; D013777:Tetrazoles; C068467:2-(4'-diethylaminophenyl)benzothiazole; C001573:5-amino-1H-tetrazole; D010165:Palladium; D004247:DNA; C427203:calf thymus DNA; D002945:Cisplatin