Anthrapyrazoles are potent cytotoxic agents that intercalate into DNA, causing DNA strand breaks, inhibition of DNA synthesis and topoisomerase II. In this study, we investigated the in vitro cytotoxic activity of two anthrapyrazole analogues (AP-10 and AP-11) in human prostate (DU-145) and testicular (NTERA-2) carcinoma cells. The cytotoxic activity of these analogues was determined using the MTS cell growth inhibition assay. The IC50 of AP-10 on NTERA-2 and DU-145 cells was found to be 0.2 and 0.4 µM, respectively. AP-11 inhibited cell growth with an IC50 value of 1.2 µM (NTERA-2) and 3.2 µM (DU-145). Using trypan blue dye exclusion assay, we were able to confirm the cytotoxic effect of AP-10 and AP-11 on DU-145 cells, thereby distinguishing it from the cytostatic effect. To determine whether cells were able to recover after exposure to the anthrapyrazole analogues, DU-145 and NTERA-2 cells were exposed to the IC50 concentration of AP-10 and AP-11. After a 1-h exposure, fresh media containing either testosterone or dihydrotestosterone were added daily for five days and the cell growth rate was compared to the control. Although cells exposed to AP-10 and AP-11 were able to recover, they never attained the growth rate observed in the control cultures. The DNA fragmentation assay did not provide evidence of apoptosis. In conclusion, our results demonstrated that AP-10 had a higher cytotoxic activity than AP-11, and apoptosis appeared not to be involved in the biological activity of these compounds.

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