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Melanoma-specific ferrocene esters of the fungal cytotoxin illudin M.

Title data

Knauer, Sebastian ; Biersack, Bernhard ; Zoldakova, Miroslava ; Effenberger-Neidnicht, Katharina ; Milius, Wolfgang ; Schobert, Rainer:
Melanoma-specific ferrocene esters of the fungal cytotoxin illudin M.
In: Anti-Cancer Drugs. Vol. 20 (September 2009) Issue 8 . - pp. 676-681.
ISSN 1473-5741
DOI: https://doi.org/10.1097/CAD.0b013e32832e056a

Abstract in another language

The unfavorable therapeutic index of the fungal cytotoxin illudin M was to be improved by covalent attachment of the redox modulator and phenyl isobiostere ferrocene. Esters of illudin M with ferrocenoic and 1,1'-ferrocenedioic acid were prepared, structurally characterised (X-ray), and tested for cytotoxicity [MTT assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], induction of apoptosis (TUNEL assay; western blotting for caspase-9), and tumor specificity in cells of human HL-60 leukemia, human 518A2 melanoma, and in nonmalignant human foreskin fibroblasts. The diester of illudin M with 1,1'-ferrocenedioic acid was distinctly more antiproliferative and apoptosis inducing in the melanoma cells [half maximal inhibitory concentration, IC50(48 h) = 0.4+/-0.1 micromol/l] than in the HL-60 cells [IC50(48 h) = 3.0+/-1.6 micromol/l] and in the nonmalignant fibroblasts [IC50(48 h) = 3.7+/-1.9 micromol/l]. This corresponds to a doubling of the therapeutic index with respect to illudin M. The monoester of illudin M with ferrocenoic acid was nine times less efficacious in the cancer cells, when compared with the diester. In conclusion, the ferrocene diminishes the general toxicity of the illudin M moiety and increases its cell line specificity. The bis(illudinyl M) 1,1'-ferrocenedioate presumably operates by a synergistic, two-pronged attack on its molecular targets.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Anorganic Chemistry I
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 23 Mar 2018 10:05
Last Modified: 23 Mar 2018 10:05
URI: https://eref.uni-bayreuth.de/id/eprint/10449