Archiv der Pharmazie, vol.348, no.7, pp.508-517, 2015 (SCI-Expanded)
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.A novel series of dithiocarbamic acid 6,11-dioxo-6,11-dihydro-1H-anthra[1,2-d]imidazol-2-yl methyl esters were synthesized and their cytotoxic and apoptotic activities were evaluated on HeLa cells. Some of these compounds showed potent cytotoxic activities and are able to induce the apoptosis mechanism in this cell line. Especially, 2c, 2d, and 2f had a high cytotoxic activity with an IC50 value of 8 or 10μM at 24h. These three compounds also induced HeLa cell apoptosis as compared to mitoxantrone. Particularly, 3μM of 2f induced a high rate of early apoptotic cells (12.9%) at 6h whereas mitoxantrone induced early apoptosis (5.5%) at 24h. Compound 2c demonstrated a high ADP/ATP ratio (9.31) in HeLa cells at 12h compared to mitoxantrone or other compounds, suggesting that 2c might induce HeLa cell apoptosis through the mitochondrial pathway. Caspase-3 activity started to increase after treatment with 6μM of 2c for 6h, and the maximal peak of activity was obtained at 12h of incubation time. All three compounds were found to be potent apoptotic inducers compared to mitoxantrone. A series of dithiocarbamic acid 6,11-dioxo-6,11-dihydro-1H-anthra[1,2-d]imidazol-2-yl methyl esters were synthesized for the first time and their cytotoxic and apoptotic activities were evaluated in HeLa cells. Compounds 2c, 2d, and 2f displayed high cytotoxic activity with IC50 values of 8-10μM at 24h.