Synthesis and Evaluation of New Dithiocarbamic Acid 6,11-Dioxo-6,11-dihydro-1H-anthra[1,2-d]-imidazol-2-yl Methyl Esters

Onder N. I., Incesu Z., ÖZKAY Y.

ARCHIV DER PHARMAZIE, no.7, pp.508-517, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2015
  • Doi Number: 10.1002/ardp.201500063
  • Journal Name: ARCHIV DER PHARMAZIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Page Numbers: pp.508-517
  • Keywords: Annexin V, Anthraquinones, Apoptosis, Cell Culture, HeLa cells, STRUCTURE-BASED DESIGN, 4(3H)-QUINAZOLINONE DERIVATIVES, ANNEXIN-V, APOPTOSIS, AGENT, CELLS
  • Anadolu University Affiliated: Yes

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 10M at 24h. These three compounds also induced HeLa cell apoptosis as compared to mitoxantrone. Particularly, 3M 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 6M 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.