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| Description
| - The main objective is to increase knowledge and understanding of the design and mechanisms of action of antitumor metallodrugs, and to use this enhanced knowledge in combination with modern genomic research to develop new classes of metallodrugs with truly novel mechanisms of action and novel spectra of biomedical activity including targeted action. Secondary objectives are: (i) to design and study transition metal-based agents that circumvent known clinical drawbacks of “conventional” cisplatin and its analogs (resistance, limited spectrum of activity, lack of specificity, side effects) through different molecular-level actions and through molecular and cellular targeting; (ii) enhance our knowledge of the molecular and macromolecular level effects of existing clinical agents and use this knowledge to underpin the process of designing new metallodrugs. Major outcome expected: New targeted 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)
- Hlavním cílem projektu je zdokonalit znalosti o mechanismech protinádorového působení metalofarmak; využít nové znalosti v kombinaci s moderním výzkumem genomu pro návrhy nových typů metalofarmak, působících zcela novými mechanismy a vykazujícími nové spektrum protinádorového působení včetně cíleného. Další cíle jsou: i) navrhnout a studovat látky odvozené od komplexů přechodných kovů, které umožní obejít známá omezení související s klinickým využitím konvenční cisplatiny a jejích analogů (resistence, omezené spektrum a nízká specificita působení, vedlejší účinky) na základě jejich odlišného působení na molekulární a buněčné úrovni včetně působení cíleného; ii) zdokonalit znalosti o efektech látek již využívaných v klinické praxi na molekulární (makromolekulární) úrovni a podpořit tak vývoj nových metalofarmak. Očekávané výstupy: Budou navržena nová (také cíleně působící) metalofarmaka a získány údaje o souvisejících biochemických, molekulárně biologických a farmakologických aspektech jejich působení tak, aby bylo možné navrhnout nové kandidáty účinnějších léčiv proti rakovině pro klinické zkoušky.
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| Title
| - Metallodrugs based on osmium, platinum and ruthenium complexes. From mechanistic studies to novel, more efficient chemotherapy of cancer (en)
- Metalofarmaka odvozená od komplexů osmia, platiny a ruthenia. Od mechanistických studií k nové, účinnější chemoterapii rakoviny
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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
| - metallodrugs cancer DNA cytotoxicity,antitumor effects mechanism (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
| - Systematic research project that aims to study pharmacology of novel anti tumorous drugs on the basis of transition metal-based complexes. Results were published in 26 manuscripts in Journals with IF e.g. NAR or J Med Chem., that belong to respected journals in the field. The project is surely very fruitful and efficiently done. (en)
- Jedná se o systematický výzkumný projekt s cílem studia farmakologie nových protinádorových léčiv na bázi komplexů přechodných kovů. Výsledky byly publikovány v celkem 26 článcích s IF mezi nimiž například NAR či J Med Chem, jež patří mezi respektovaná periodika v daném oboru. Jedná se jistě o velmi přínosný až příkladný projekt. (cs)
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| http://linked.open...tniCyklusProjektu
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| http://linked.open.../cep/klicoveSlovo
| - metallodrugs cancer DNA cytotoxicity
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| is http://linked.open...vavai/riv/projekt
of | - Different affinity of nuclear factor-kappa B proteins to DNA modified by antitumor cisplatin and its clinically ineffective trans isomer
- Thermodynamics of translesion synthesis across a major DNA adduct of antitumor oxaliplatin: Differential scanning calorimetric study
- The thermodynamics of translesion DNA synthesis past major adducts of enantiomeric analogues of antitumor cisplatin
- Thermodynamic and mechanistic insights into translesion DNA synthesis catalyzed by Y-family DNA polymerase across a bulky double-base lesion of an antitumor platinum drug
- Thermodynamic stability and energetics of DNA duplexes containing major intrastrand cross-links of second-generation antitumor dinuclear Pt-II complexes
- Activation of trans geometry in bifunctional mononuclear platinum complexes by a non-bulky methylamine ligand
- Insight into the toxic effects of cis-dichloridoplatinum(II) complexes containing 7-azaindole halogeno derivatives in tumor cells
- 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
- Functionalization of osmium arene anticancer complexes with (poly)arginine: Effect on cellular uptake, internalization, and cytotoxicity
- 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)]
- Cellular response to antitumor cis-dichlorido platinum(II) complexes of CDK inhibitor bohemine and its analogues
- Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity
- Interactions of DNA with a new platinum(IV) azide dipyridine complex activated by UVA and visible light: Relationship to toxicity in tumor cells
- Mechanistic insights into toxic effects of a benzotriazolate-bridged dinuclear platinum(II) compound in tumor cells
- Diazido Mixed-Amine Platinum(IV) Anticancer Complexes Activatable by Visible-Light Form Novel DNA Adducts
- Antitumor carboplatin is more toxic in tumor cells when photoactivated: enhanced DNA binding
- How to modify 7-azaindole to form cytotoxic Pt(II) complexes: Highly in vitro anticancer effective cisplatin derivatives involving halogeno-substituted 7-azaindole
- Spontaneous Translocation of Antitumor Oxaliplatin, its Enantiomeric Analogue, and Cisplatin from One Strand to Another in Double-Helical DNA
- Organometallic Half-Sandwich Iridium Anticancer Complexes
- Combined theoretical and computational study of interstrand DNA guanine-guanine cross-linking by trans-[Pt(pyridine)2] derived from the photoactivated prodrug trans,trans,trans-[Pt(N3)2(OH)2(pyridine)2]
- DNA conformation and repair of polymeric natural DNA damaged by antitumor azolato-bridged dinuclear PtII complex
- Different features of the DNA binding mode of antitumor cis-amminedichlorido(cyclohexylamine)platinum(II) (JM118) and cisplatin in vitro
- DNA Interstrand Cross-Links of an Antitumor Trinuclear Platinum(II) Complex: Thermodynamic Analysis and Chemical Probing
- Valuable insight into the anticancer activity of the platinum-histone deacetylase inhibitor conjugate, cis-[Pt(NH3)2malSAHA-2H)]
- Recognition of DNA bulges by dinuclear iron(II) metallosupramolecular helicates
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| is http://linked.open...vavai/cep/projekt
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