Synthesis of 1,11-Dihydro-2H-[1,3]oxazolo[4′,5′:5,6]indeno[1,2-b]quinolin-2-ones with Potential Topoisomerase I Inhibitory Activity

Delot Marc. Carato Pascal. Furman Christophe. Lemoine Amélie. Lebegue Nicolas. Berthelot Pascal. Yous Saïd. Synthesis  2009,  3819 

In the discussion of the bioassay results, the substrate concentrations were incorrectly given in M rather than in µM. The same error appeared in the experimental section. The corrected paragraphs are given here.

The effects of compounds 18a-h on the proliferation of DU145 human androgen-independent prostate cancer cells were assayed in triplicate by using a standard incubation time of 72 h. Compounds 18a, 18f, and 18d and showed a weak activity, with an inhibition of proliferation of 5% at 10 µM, whereas compounds 18b, 18c, 18e, 18g, and 18h showed no activity with these resistant cells at this concentration. These results could be the result of several factors, such as the poor solubility of the compounds tested and their poor cellular uptake, which is related to their high values of logP, which were calculated theoretically to be between 3.7  0.4 and 5.6  0.4.

Cell Culture and Cell Proliferation Assay

Human prostate DU145 cancer cells were grown at 37 C in RPMI 1640 medium supplemented with 10% fetal calf serum, in a humidified incubator under 5% CO2. In the cell-proliferation assay, cells were plated (3200 cells/well) on 96-well plates. After 3 days, the cell medium was changed to serum-free medium, and the cells were starved for 24 h for culture synchronization. Cells were then incubated in a culture medium that contained 10 µM of the test compound dissolved in less than 0.1% DMSO. After incubation for 72 h, cell growth was estimated by means of the colorimetric MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test.