2. Academic Validation
  3. The structure of anthracycline derivatives determines their subcellular localization and cytotoxic activity

The structure of anthracycline derivatives determines their subcellular localization and cytotoxic activity

  • ACS Med Chem Lett. 2013 Feb 4;4(3):323-8. doi: 10.1021/ml3002852.
Pazit Shaul 1,  Michael Frenkel 2,  Elinor Briner Goldstein 1,  Leonid Mittelman 2,  Assaf Grunwald 1,  Yuval Ebenstein 1,  Ilan Tsarfaty 3,  Micha Fridman 1
Affiliations

Affiliations

  • 1 Department of Organic Chemistry and Department of Chemical Physics, School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University , Ramat Aviv 69978, Tel Aviv, Israel.
  • 2 Department of Clinical Microbiology and Immunology and Sackler Cellular and Molecular Imaging Center, Sackler School of Medicine, Tel Aviv University , Ramat Aviv 69978, Tel Aviv, Israel.
  • 3 Department of Clinical Microbiology and Immunology and Sackler Cellular and Molecular Imaging Center, Sackler School of Medicine, Tel Aviv University , Ramat Aviv 69978, Tel Aviv, Israel ; Department of Clinical Microbiology and Immunology and Sackler Cellular and Molecular Imaging Center, Sackler School of Medicine, Tel Aviv University , Ramat Aviv 69978, Tel Aviv, Israel.
PMID: 24900668 DOI: 10.1021/ml3002852
Abstract

The cytotoxic activities and subcellular localizations of clinically used and synthetic analogues of the anthracycline family of chemotherapeutic agents were studied. The structures of the anthracycline derivatives affected their cytotoxicity and the time required for these compounds to exert cytotoxic effects on tumor cells. Fluorescent DNA intercalator displacement experiments demonstrated that there was no correlation between the DNA intercalation properties and the cytotoxicity of the studied anthracycline derivatives. Confocal microscopy experiments indicated that structural differences led to differences in subcellular localization. All studied anthracycline derivatives were observed in lysosomes, suggesting that this organelle, which is involved in several processes leading to malignancy, may contain previously unidentified molecular targets for these antitumor agents.

Keywords

anthracyclines; antitumor agents; cytotoxic activity; subcellular localization.

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