Antitumor Effects of a New Retinoate of the Fungal Cytotoxin Illudin M in Brain Tumor Models.

While the fungal metabolite illudin M () is indiscriminately cytotoxic in cancer and non-malignant cells, its retinoate showed a greater selectivity for the former, especially in a cerebral context. Illudin M killed malignant glioma cells as well as primary neurons and astrocytes at similarly low concentrations and destroyed their microtubule and glial fibrillary acidic protein (GFAP) networks. In contrast, the ester was distinctly more cytotoxic in highly dedifferentiated U87 glioma cells than in neurons, which were even stimulated to enhanced growth.

Lipophilic Pt(II) complexes with selective efficacy against cisplatin-resistant testicular cancer cells.

A series of dichloridoplatinum(II) complexes with selective and high cytotoxicity [IC(90)(96h)≤3 μM] against cisplatin-resistant 1411HP testicular cancer cells were identified. They bear stationary 6-aminomethylnicotinate or 2,4-diaminobutyrate ligands esterified with lipophilic terpenyl residues, i.e.

Effects of a combretastatin A4 analogous chalcone and its Pt-complex on cancer cells: A comparative study of uptake, cell cycle and damage to cellular compartments.

The combretastatin A4 analogous chalcone (2E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 1 and its dichloridoplatinum(II) (6-aminomethylnicotinate) complex 2 were previously found to be highly active against a variety of cancer cell lines while differing in their apoptosis induction and long-term regrowth retardation (Schobert et al. [1]). Further differences were identified now.

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

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.

Pt(II) complexes of a combretastatin A-4 analogous chalcone: effects of conjugation on cytotoxicity, tumor specificity, and long-term tumor growth suppression.

Three dichlorido(6-aminomethylnicotinate)platinum complexes 6 comprising a combretastatin A-4 analogous chalcone were tested on a panel of 21 tumor cell lines from 9 entities. Parent chalcone 1a and the directly linked conjugate 6a exhibited excellent antiproliferative activities, similar in magnitude [average log(IC(50)) values of -7.3 (1a) and -7.

Terpene conjugates of diaminedichloridoplatinum(II) complexes: antiproliferative effects in HL-60 leukemia, 518A2 melanoma, and HT-29 colon cancer cells.

Twenty-eight [6-(aminomethyl)nicotinate]dichloridoplatinum(II) complexes 1 esterified with various terpene alcohols either directly or via alkyl spacers were tested for antiproliferative activity in human 518A2 melanoma and HL-60 leukemia cells. Generally, conjugates with menthanes and polycyclic sesquiterpenes attached via propane-1,2-diyl spacers were most active. In the melanoma cells, the propane-1,2-diyl-spacered conjugates of (-)-menthol (1a(2')), (+)-neomenthol (1b(2')), (-)-carvomenthol (1h(2')), and (-)-isolongifolol (1n(2')) displayed growth inhibition at IC(50)<4 microM which is ten times smaller than that of cisplatin.