Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
Arch Pharm (Weinheim). 2015 Jul;348(7):508-17. doi: 10.1002/ardp.201500063. Epub 2015 May 21.
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 10 μM at 24 h. These three compounds also induced HeLa cell apoptosis as compared to mitoxantrone. Particularly, 3 μM of 2f induced a high rate of early apoptotic cells (12.9%) at 6 h whereas mitoxantrone induced early apoptosis (5.5%) at 24 h. Compound 2c demonstrated a high ADP/ATP ratio (9.31) in HeLa cells at 12 h 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 6 μM of 2c for 6 h, and the maximal peak of activity was obtained at 12 h of incubation time. All three compounds were found to be potent apoptotic inducers compared to mitoxantrone.
合成了一系列新型的二硫代氨基甲酸 6,11-二氧代-6,11-二氢-1H-蒽[1,2-d]咪唑-2-基甲酯，并评估了它们对 HeLa 细胞的细胞毒性和促凋亡活性。其中一些化合物表现出很强的细胞毒性，并能够诱导该细胞系中的凋亡机制。特别是 2c、2d 和 2f 在 24 小时时具有 8 或 10 μM 的高细胞毒性 IC50 值。与米托蒽醌相比，这三种化合物还能诱导 HeLa 细胞凋亡。特别是 2f 在 6 小时时诱导了高达 12.9%的早期凋亡细胞（early apoptotic cells），而米托蒽醌在 24 小时时诱导了 5.5%的早期凋亡。与米托蒽醌或其他化合物相比，化合物 2c 在 HeLa 细胞中在 12 小时时表现出高 ADP/ATP 比（9.31），表明 2c 可能通过线粒体途径诱导 HeLa 细胞凋亡。用 6 μM 的 2c 处理 6 小时后，半胱天冬酶-3 的活性开始增加，在孵育 12 小时时达到最大活性峰值。与米托蒽醌相比，这三种化合物都被发现是有效的促凋亡诱导剂。
