Studies on activities, cell uptake and DNA binding of four trans-planaramineplatinum(II) complexes of the form: trans-PtL(NH3)Cl2, where L=2-hydroxypyridine, imidazole, 3-hydroxypyridine and imidazo(1,2-alpha)pyridine

Four trans-planaramineplatinum(II) complexes code named YH9, YH10, YH11 and YH12 each of the form trans-PtL(NH(3))Cl(2), where L=2-hydroxypyridine and 3-hydroxypyridine, imidazole, and imidazo(1,2-alpha)pyridine for YH9, YH10, YH11 and YH12, respectively, have been synthesized and the activity of th...

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Bibliographic Details
Published in:Journal of inorganic biochemistry 2004-08, Vol.98 (8), p.1261-1270
Main Authors: Huq, Fazlul, Yu, Jun Qing, Daghriri, Hassan, Beale, Philip
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Cell Line, Tumor - drug effects
DNA - chemistry
DNA - metabolism
Humans
Imidazoles - chemistry
Imidazoles - metabolism
Ligands
Molecular Structure
Nucleic Acid Conformation
Organoplatinum Compounds - chemistry
Organoplatinum Compounds - metabolism
Organoplatinum Compounds - pharmacology
Pyridines - chemistry
Pyridines - metabolism
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Summary:Four trans-planaramineplatinum(II) complexes code named YH9, YH10, YH11 and YH12 each of the form trans-PtL(NH(3))Cl(2), where L=2-hydroxypyridine and 3-hydroxypyridine, imidazole, and imidazo(1,2-alpha)pyridine for YH9, YH10, YH11 and YH12, respectively, have been synthesized and the activity of the compounds against human cancer cell lines, cell uptake, DNA-binding and nature of interaction with pBR322 plasmid DNA have been studied. The compound having imidazo(1,2-alpha)pyridine ligand as one the carrier ligands in the trans-configuration is found to be significantly more active than cis-platin against ovarian A2780(cisR) cancer cell line corresponding with higher Pt-DNA binding. All other compounds have resistance factors less than that for cis-platin in the A2780 and A2780(cisR) cell lines. A greater prevention of BamH1 digestion with increasing concentration of the compounds indicates that as the compounds bind with nucleobases in DNA, the DNA conformation is changed sufficiently so as to prevent BamH1 digestion at the specific GG site. Gel electrophoresis results also indicate that as the compounds bind to DNA, unwinding of supercoiled form I DNA takes place to change it from the negatively supercoiled form I through relaxed circular form I to the positively supercoiled form I.
ISSN:0162-0134
1873-3344
DOI:10.1016/j.jinorgbio.2004.05.014