Jana Kasparkova

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DNA-protein cross-links are formed by various DNA-damaging agents including antitumor platinum drugs. The natures of these ternary DNA-Pt-protein complexes (DPCLs) can be inferred, yet much remains to be learned about their structures and mechanisms of formation. We investigated the origin of these DPCLs and their cellular processing on molecular level(More)
When antitumor platinum drugs react with DNA they form various types of intrastrand and interstrand cross-links (CLs). One class of new antitumor platinum compounds comprises bifunctional PtII compounds based on the dinuclear or trinuclear geometry of leaving ligands. It has been shown that the DNA-binding modes of dinuclear or trinuclear bifunctional PtII(More)
A new synthetic isothiocyanate (ITC) derivative, ethyl 4-isothiocyanatobutanoate (E-4IB), appeared to be an effective modulator of cellular proliferation and potent inducer of apoptosis. In cooperation with cisplatin, this compound exerted synergistic effects in human ovarian carcinoma A2780 cells. In the present study we investigated in more detail(More)
Replacement of one ammine in clinically ineffective trans-[PtCl2(NH3)2] (transplatin) by a planar N-heterocycle, thiazole, results in significantly enhanced cytotoxicity. Unlike 'classical' cisplatin {cis-[PtCl2(NH3)2]} or transplatin, modification of DNA by this prototypical cytotoxic transplatinum complex trans-[PtCl2(NH3)(thiazole)] (trans-PtTz) leads to(More)
The effect of replacement of the N,N-chelating ligand 1,10-phenanthroline (phen) in the Ir(III) pentamethylcyclopentadienyl (Cp*) complex [(η(5)-Cp*)(Ir)(phen)Cl](+) (2) with the C,N-chelating ligand 7,8-benzoquinoline (bq) to give [(η(5)-Cp*)(Ir)(bq)Cl] (1) on the cytotoxicity of these Cp*Ir(III) complexes toward cancer cell lines was investigated. Complex(More)
The new platinum(IV) complex cis,trans,cis-[PtCl(2)(CH(3)COO)(2)-(NH(3))(1-adamantylamine)] [adamplatin(IV)] seems promising for the perspective application in therapy of corresponding tumors. It is therefore of great interest to understand details of mechanisms underlying its biological efficacy. Cellular uptake of the drug, alterations in the target DNA(More)
The moderate-to-high in vitro cytotoxicity against ovarian A2780 (IC50 = 4.7-14.4 μM), prostate LNCaP (IC50 = 18.7-30.8 μM) and prostate PC-3 (IC50 = 17.6-42.3 μM) human cancer cell lines of the platinum(II) cyclobutane-1,1'-dicarboxylato complexes [Pt(cbdc)(naza)2] (1-6; cbdc = cyclobutane-1,1'-dicarboxylate(2-); naza = halogeno-substituted 7-azaindoles),(More)
The cisplatin analogues cis-[PtCl2(3ClHaza)2] (1) and cis-[PtCl2(3IHaza)2] (2) (3ClHaza and 3IHaza are 3-chloro-7-azaindole and 3-iodo-7-azaindole, respectively) are quite toxic to ovarian tumor cells, with moderately better IC50 values than for cisplatin in the cisplatin-sensitive cell line A2780. We investigated potential factors which might be involved(More)
Platinum diam(m)ine complexes, such as cisplatin, are successful anticancer drugs, but suffer from problems of resistance and side-effects. Photoactivatable Pt(IV) prodrugs offer the potential of targeted drug release and new mechanisms of action. We report the synthesis, X-ray crystallographic and spectroscopic properties of photoactivatable diazido(More)
The trinuclear BBR3464 ([{trans-PtCl(NH(3))(2)}(2)µ-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2))](4+)) belongs to the polynuclear class of platinum-based anticancer agents. DNA adducts of this complex differ significantly in structure and type from those of clinically used mononuclear platinum complexes, especially, long-range (Pt, Pt) intrastrand and(More)