Structural characterization and DNA interactions of new cytotoxic transplatin analogues containing one planar and one nonplanar heterocyclic amine ligand.

NAJAJREH, Yousef, Jana KAŠPÁRKOVÁ, María Victoria MARINI PALOMEQUE, Dan GIBSON a Viktor BRABEC. Structural characterization and DNA interactions of new cytotoxic transplatin analogues containing one planar and one nonplanar heterocyclic amine ligand. Journal of Biological Inorganic Chemistry. Germany: Springer Berlin / Heidelberg, 2005, roč. 10, č. 7, s. 722-731. ISSN 0949-8257.

Základní údaje

Originální název

Structural characterization and DNA interactions of new cytotoxic transplatin analogues containing one planar and one nonplanar heterocyclic amine ligand.

Název česky

Strukturni charakterizace a interakce s DNA novych cytotoxickych transplatinovych analogu

Autoři

NAJAJREH, Yousef (275 Palestina), Jana KAŠPÁRKOVÁ (203 Česká republika), María Victoria MARINI PALOMEQUE (858 Uruguay), Dan GIBSON (376 Izrael) a Viktor BRABEC (203 Česká republika, garant)

Vydání

Journal of Biological Inorganic Chemistry, Germany, Springer Berlin / Heidelberg, 2005, 0949-8257

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Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.224

Kód RIV

RIV/00216224:14310/05:00035838

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000233238600002

Klíčová slova česky

Platina; DNA; retezcove mustky; cytotoxicita; rentgenová krystalografie

Klíčová slova anglicky

Platinum ; DNA ; Cross-links ; Cytotoxicity ; X-ray crystallography

Štítky

Cross-links, cytotoxicity, DNA, platinum, X-ray crystallography

Příznaky

Mezinárodní význam, Recenzováno

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Anotace

V originále

trans-Diaminedicholoroplatinum(II) complexes with one planar and one non-planar heterocyclic amine ligand were designed as new potential antitumor drugs. The X-ray crystallographic structures of trans-[PtCl2(4-picoline)(piperidine)] and trans-[PtCl2(4-picoline)(piperazine)]-HCl revealed that the piperidine and piperazine ligands bind to the platinum through the equatorial position and that the ligands adopt the chair conformation. The nonplatinated amine of the piperazine can form hydrogen bonds with atoms that are approximately 7.5 angstrom away from the Pt binding site. DNA is considered a major pharmacological target of platinum compounds. Hence, to expand the database correlating structural features of platinum compounds and DNA distortions induced by these compounds, which may facilitate identification of more effective anticancer platinum drugs, we describe the DNA binding mode in a cell-free medium of trans-[PtCl2(4-picoline)(piperidine)] and trans-[PtCl2(4-picoline)(piperazine)]-HCl. Interestingly, the overall impact of the replacement of the second ammine group in transplatin by the heterocyclic ligands appears to change the character of the global conformational changes induced in DNA towards that induced by cisplatin. The clinical ineffectiveness of the parent transplatin has been proposed to be also associated with its reduced capability to form bifunctional adducts in double-helical DNA. The results of the present work support the view that replacement of both ammine groups of transplatin by heterocyclic ligands enhances cytotoxicity probably due to the marked enhancement of the stability of intrastrand cross-links in double-helical DNA.

Česky

trans-Diaminedicholoroplatinum(II) komplexy s jedním planárním a jedním neplanarním heterocyklickým aminovým lingandem byli navrženy jako nové potenciální protinadorové léky.