title: Novel antitumor cisplatin and transplatin derivatives containing 1-methyl-7-azaindole: synthesis, characterization, and cellular responses.
abstract: The current work investigates the effect of new bifunctional and mononuclear Pt(II) compounds, the cis- and trans-isomers of [PtCl2(NH3)(L)] (L = 1-methyl-7-azaindole, compounds 1 and 2, respectively), on growth and viability of human carcinoma cells as well as their putative mechanism(s) of cytotoxicity. The results show that substitution of 1-methyl-7-azaindole for ammine in cisplatin or transplatin results in an increase of the toxic efficiency, selectivity for tumor cells in cisplatin-resistant cancer cells, and activation of the trans geometry. The differences in the cytotoxic activities of 1 and 2 were suggested to be due to their different DNA binding mode, different capability to induce cell cycle perturbations, and fundamentally different role of transcription factor p53 in their mechanism of action. Interestingly, both isomers make it possible to detect their cellular uptake and distribution in living cells by confocal microscopy without their modification with an optically active tag.
authors.affiliation: Department of Biophysics, Centre of the Region Hana for Biotechnological and Agricultural Research, Palacky University , Slechtitelu 11, 783 41 Olomouc, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Pracharova
authors.forename: Teresa
authors.initials: T
authors.lastname: Saltarella
authors.forename: Tereza
authors.initials: T
authors.lastname: Radosova Muchova
authors.forename: Simone
authors.initials: S
authors.lastname: Scintilla
authors.forename: Vojtech
authors.initials: V
authors.lastname: Novohradsky
authors.forename: Olga
authors.initials: O
authors.lastname: Novakova
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Intini
authors.forename: Concetta
authors.initials: C
authors.lastname: Pacifico
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
authors.forename: Petr
authors.initials: P
authors.lastname: Ilik
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
authors.forename: Jana
authors.initials: J
authors.lastname: Kasparkova
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives*; D004247:DNA / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C023422:7-azaindole dimer; D000970:Antineoplastic Agents; D007211:Indoles; D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53; C034697:transplatin; D004247:DNA; D002945:Cisplatin