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Synthesis and Evaluation of New Dithiocarbamic Acid 6,11‐Dioxo‐6,11‐dihydro‐1 H ‐anthra[1,2‐ d ]‐imidazol‐2‐yl Methyl Esters
Author(s) -
Onder Nur İpek,
İncesu Zerrin,
Özkay Yusuf
Publication year - 2015
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201500063
Subject(s) - chemistry , stereochemistry , medicinal chemistry
A novel series of dithiocarbamic acid 6,11‐dioxo‐6,11‐dihydro ‐ 1 H ‐ 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 IC 50 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.