A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: a Dual-Acting Weapon for Targeting DNA in Cancer Cells
In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, , which was thoroughly characterized by means of spectroscopic and spectrometric techniques. Tested towards a panel of various human tumor cell lines, this compound showed superior in vitro antitu...
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Published in | International journal of molecular sciences Vol. 19; no. 12; p. 3775 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
27.11.2018
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug,
, which was thoroughly characterized by means of spectroscopic and spectrometric techniques. Tested towards a panel of various human tumor cell lines, this compound showed superior in vitro antitumor potential than the reference drug cisplatin. In addition, an antitumor potential of
was found, which is comparable to that of oxaliplatin in 3D spheroid models of colon cancer cells. Mechanistic studies performed in colon cancer cells confirmed that the conjugation of chlorambucil to Pt(IV) cisplatin-based scaffold tunes the lipophilicity of the prodrug, consequently improving the ability of the compound to accumulate into cancer cells and to target DNA, ultimately leading to apoptotic cancer cell death. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms19123775 |