We have carried out a cell-based screen aimed at discovering small molecules that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochemical assays, and target validation studies in mammalian cells, we show… (More)
A series of stilbenes, based on combretastatin A-4, were synthesised. A structure-activity study was carried out to characterise the interaction of these agents with tubulin. The substitution of small alkyl substituents for the 4'-methoxy group of combretastatin A-4 and the loss of the 3'-hydroxyl group does not have a major effect on the interaction with… (More)
CYP2S1 is an extrahepatic cytochrome P450 (P450) that shows marked individuality in constitutive and inducible expression. CYP2S1 mRNA expression is increased in psoriasis and by treatments for psoriasis, including retinoids and UV radiation, although endogenous substrates remain poorly characterized. Because previous model systems have overexpressed… (More)
Platinum diam(m)ine complexes, such as cisplatin, are successful anticancer drugs, but suffer from problems of resistance and side-effects. Photoactivatable Pt(IV) prodrugs offer the potential of targeted drug release and new mechanisms of action. We report the synthesis, X-ray crystallographic and spectroscopic properties of photoactivatable diazido… (More)
BACKGROUND There are unpredictable inter-individual differences in sensitivity to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we hypothesised that variability in cutaneous P450 expression may influence PUVA sensitivity. We previously showed that P450… (More)
Photoactivatable Pt IV diazido complexes have unusual photobiologic properties. We show here that trans, trans,trans-[Pt IV (N 3) 2 (OH) 2 (py)(NH 3)] complex 3 is a potent photoactivated cytotoxin toward human cancer cells in culture, with an average IC 50 value in 13 cell lines of 55 AE 28 mmol/L after 30 minutes (0.12 mW/cm 2) photoactivation with UVA,… (More)
A new anticancer agent based on the conjugation of a photoactivatable Pt(IV) pro-drug to a cyclic RGD-containing peptide is described. Upon visible light irradiation, phototoxicity was induced preferentially in SK-MEL-28 melanoma cancer cells overexpressing αVβ3 integrin compared to control DU-145 human prostate carcinoma cells.