当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Conformation and recognition of DNA damaged by antitumor cis-dichlorido platinum(II) complex of CDK inhibitor bohemine.

Conformation and recognition of DNA damaged by antitumor cis-dichlorido platinum(II) complex of CDK inhibitor bohemine.

Abstract：

:A substitution of the ammine ligands of cisplatin, cis-[Pt(NH3)2Cl2], for cyclin dependent kinase (CDK) inhibitor bohemine (boh), [2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine], results in a compound, cis-[Pt(boh)2Cl2] (C1), with the unique anticancer profile which may be associated with some features of the damaged DNA and/or its cellular processing (Travnicek Z et al. (2003) J Inorg Biochem94, 307-316; Liskova B (2012) Chem Res Toxicol25, 500-509). A combination of biochemical and molecular biology techniques was used to establish mechanistic differences between cisplatin and C1 with respect to the DNA damage they produce and their interactions with critical DNA-binding proteins, DNA-processing enzymes and glutathione. The results show that replacement of the NH3 groups in cisplatin by bohemine modulates some aspects of the mechanism of action of C1. More specifically, the results of the present work are consistent with the thesis that, in comparison with cisplatin, effects of other factors, such as: (i) slower rate of initial binding of C1 to DNA; (ii) the lower efficiency of C1 to form bifunctional adducts; (iii) the reduced bend of longitudinal DNA axis induced by the major 1,2-GG intrastrand cross-link of C1; (iv) the reduced affinity of HMG domain proteins to the major adduct of C1; (v) the enhanced efficiency of the DNA adducts of C1 to block DNA polymerization and to inhibit transcription activity of human RNA pol II and RNA transcription; (vi) slower rate of the reaction of C1 with glutathione, may partially contribute to the unique activity of C1.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Novakova O,Liskova B,Vystrcilova J,Suchankova T,Vrana O,Starha P,Travnicek Z,Brabec V

doi

10.1016/j.ejmech.2014.03.041

subject

Has Abstract

pub_date

2014-05-06 00:00:00

pages

54-64

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(14)00254-2

journal_volume

78

pub_type

杂志文章

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