title: Synthesis and evaluation of new dithiocarbamic acid 6,11-dioxo-6,11-dihydro-1H-anthra[1,2-d]-imidazol-2-yl methyl esters.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
authors.forename: Nur İpek
authors.initials: Nİ
authors.lastname: Onder
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
authors.forename: Zerrin
authors.initials: Z
authors.lastname: İncesu
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Özkay
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D013859:Thiocarbamates
keywords: Annexin V; Anthraquinones; Apoptosis; Cell Culture; HeLa cells