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| Description
| - Hlavním cílem projektu je rozšířit znalosti o mechanismu působení světlocitlivých protinádorově účinných sloučenin kovů a využít takto získaných znalostí k vývoji nových tříd metalofarmak se zcela novým mechanismem působení a spektrem biologické účinnosti. Budou navrženy a studovány světlem aktivovatelné komplexy přechodných kovů, schopné překonat nevýhody spojené s klinickou aplikací konvenčního cytostatika cisplatiny a jejích analog (rezistence, omezené spektrum protinádorové aktivity, nízká specificita, vedlejší účinky) díky odlišnému působení na molekulární úrovni, a takto získané poznatky budou využity k racionalizaci procesu navrhování nových metalofarmak. Hlavní očekávané výsledky: budou navrženy nové, světlem aktivovatelné komplexy kovů včetně vytvoření teoretického zázemí zahrnující biochemické, molekulárně biologické a farmakologické aspekty působení těchto komplexů s cílem navrhnout nové a účinnější kandidáty léčiv pro klinické zkoušky.
- The main objective is to increase knowledge and understanding of the design and mechanisms of action of photoactivatable antitumour metallodrugs, and to use this enhanced knowledge to develop new classes of metallodrugs with truly novel mechanisms of action and novel spectra of biomedical activity. Secondary objectives are to design and study photoactivatable transition metal-based agents that circumvent known clinical drawbacks of %22conventional%22 antitumor cisplatin and its analogs (resistance, limited spectrum of activity, lack of specificity, side-effects) through different molecular-level actions and use this knowledge to underpin the process of designing new metallodrugs. Major outcome expected: new photoactivatable metallodrugs will be proposed and the associated biochemistry, molecular biology and pharmacology will be developed and examined to bring novel and more effective drug candidates to clinical trials. (en)
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| Title
| - Mechanistic studies related to targeted cancer chemotherapy with light-activated platinum and ruthenium antitumor agents (en)
- Mechanistické studie mající vztah k cílené chemoterapii rakoviny pomocí komplexů platiny a ruthenia aktivovatelných světlem
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| skos:notation
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| http://linked.open...avai/cep/aktivita
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| http://linked.open...kovaStatniPodpora
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| http://linked.open...ep/celkoveNaklady
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| http://linked.open...datumDodatniDoRIV
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| http://linked.open...i/cep/druhSouteze
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| http://linked.open...ep/duvernostUdaju
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| http://linked.open.../cep/fazeProjektu
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| http://linked.open...ai/cep/hlavniObor
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| http://linked.open...hodnoceniProjektu
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| http://linked.open...vai/cep/kategorie
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| http://linked.open.../cep/klicovaSlova
| - cancer chemotherapy; photoactivatable metallodrugs; DNA damage; photodynamic therapy; platinum; ruthenium; cisplatin (en)
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| http://linked.open...ep/partnetrHlavni
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| http://linked.open...inujicichPrijemcu
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| http://linked.open...cep/pocetPrijemcu
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| http://linked.open...ocetSpoluPrijemcu
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| http://linked.open.../pocetVysledkuRIV
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| http://linked.open...enychVysledkuVRIV
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| http://linked.open...lneniVMinulemRoce
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| http://linked.open.../prideleniPodpory
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| http://linked.open...iciPoslednihoRoku
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| http://linked.open...atUdajeProjZameru
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| http://linked.open.../vavai/cep/soutez
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| http://linked.open...usZobrazovaneFaze
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| http://linked.open...ai/cep/typPojektu
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| http://linked.open...ep/ukonceniReseni
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| http://linked.open.../cep/vedlejsiObor
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| http://linked.open...ep/zahajeniReseni
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| http://linked.open...jektu+dodavatelem
| - Výsledky dosažené v rámci tohoto projektu rozšířily teoretické znalosti o mechanismu protinádorových účinků světlem aktivovatelných sloučenin přechodných kovů. Výsledky také umožnily navrhnout nové sloučeniny jako kandidáty pro fotodynamickou terapii. (cs)
- The results obtained within this project extend theoretical background on the mechanism of antitumor effects of photoactivatable transition metal-based compounds. The results made it possible to design new compounds for photodynamic therapy. (en)
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| http://linked.open...tniCyklusProjektu
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| http://linked.open.../cep/klicoveSlovo
| - cancer chemotherapy
- DNA damage
- photoactivatable metallodrugs
- photodynamic therapy
- platinum
- ruthenium
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| is http://linked.open...vavai/riv/projekt
of | - Interaction of dinuclear ruthenium(II) supramolecular cylinders with DNA: sequence-specific binding, unwinding, and photocleavage
- Energetics, conformation, and recognition of DNA duplexes modified by methylated analogues of [PtCl(dien)]+
- DNA adducts of antitumor cisplatin preclude telomeric sequences from forming G quadruplexes
- Studies of the mechanism of action of platinum(II) complexes with potent cytotoxicity in human cancer cells
- Factors affecting DNA-DNA interstrand cross-links in the antiparallel 3'-3' sense: A comparison with the 5'-5' directional isomer
- Mechanistic studies of the modulation of cleavage activity of topoisomerase I by DNA adducts of mono- and bi-functional Pt-II complexes
- Role of DNA repair in antitumour effects of platinum drugs
- Studies on cellular accumulation of satraplatin and its major metabolite JM118 and their interactions with glutathione
- Mechanistic insights into antitumor effects of new dinuclear cis PtII complexes containing aromatic linkers
- Influence of pyridine versus piperidine ligands on the chemical, DNA binding and cytotoxic properties of light activated trans,trans,trans-[Pt(N3)2(OH)2(NH3)(L)]
- Walking of antitumor bifunctional trinuclear Pt II complex on double-helical DNA
- Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin
- DNA photocleavage by DNA and DNA-LNA amino acid-dye conjugates
- Different features of the DNA binding mode of antitumor cis-amminedichlorido(cyclohexylamine)platinum(II) (JM118) and cisplatin in vitro
- Cytotoxicity, cellular uptake, glutathione and DNA interactions of an antitumor large-ring PtII chelate complex incorporating the cis-1,4-diaminocyclohexane carrier ligand
- A metal-free DNA nuclease based on a cyclic peptide scaffold
- Cytotoxicity, cellular uptake, and DNA interactions of new monodentate ruthenium(II) complexes containing terphenyl arenes
- The contrasting chemistry and cancer cell cytotoxicity of bipyridine and bipyridinediol ruthenium(II) arene complexes
- DNA and glutathione interactions in cell-free media of asymmetric platinum(II) complexes cis- and trans-[PtCl2(isopropylamine)(1-methylimidazole)]: relations to their different antitumor effects
- DNA Interstrand Cross-Links of an Antitumor Trinuclear Platinum(II) Complex: Thermodynamic Analysis and Chemical Probing
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| is http://linked.open...vavai/cep/projekt
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