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A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: a Dual-Acting Weapon for Targeting DNA in Cancer Cells.

ABSTRACT: In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, 1, 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 1 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.

SUBMITTER: Montagner D

PROVIDER: S-EPMC6321036 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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A Pt(IV) Prodrug Combining Chlorambucil and Cisplatin: a Dual-Acting Weapon for Targeting DNA in Cancer Cells.

Montagner Diego D Tolan Dina D Andriollo Emma E Gandin Valentina V Marzano Cristina C

International journal of molecular sciences 20181127 12

In this study, two DNA-targeting agents, cisplatin and chlorambucil, were combined in a Pt(IV) prodrug, 1, 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 1 was found, which is comparable to that of oxaliplatin in 3D spheroid models of colon cancer cel ...[more]

PMID: 30486477

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Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment.

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| S-EPMC8774041 | biostudies-literature

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| S-EPMC4916484 | biostudies-literature

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