Cytotoxic Effects of a Novel Thialo Benzene Derivative 2,4-Dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) in L929 Cells

Int J Toxicol. 2014 Jul;33(4):319-324. doi: 10.1177/1091581814530437. Epub 2014 May 6.

Abstract

The aim of this study was to compare the cytotoxic effects of a newly synthesized thialo benzene derivative 2,4-dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) and a well-known antifungal agent, fluconazole, in L929 cells. L929 cells were treated with 250, 500, or 1000 µg/mL of C18H12S2IBr and with the same doses of fluconazole. Cytotoxicity tests including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, and protein content were compared. Glucose and lactate concentrations were measured to determine alterations in metabolic activity. Apoptosis was investigated by TUNEL test and results were supported with survivin enzyme-linked immunosorbent assay. Treatment with C18H12S2IBr resulted in a concentration-dependent cytotoxicity as indicated by MTT, LDH leakage assay, and decreased protein concentration. The loss of cell viability and the increased LDH leakage in 500 µg/mL and 1000 µg/mL C18H12S2IBr and fluconazole groups indicated cell membrane damage and necrotic cell death. In all groups, metabolic activities were altered but apoptosis was not induced. We have previously investigated lower doses of C18H12S2IBr; there was no cytotoxicity in L929 cells. In this study, higher doses caused cytotoxicity and alterations in metabolic activity . When we consider the similar results obtained from fluconazole and especially the lowest dose of C18H12S2IBr, this newly synthesized compound may be a good alternative antifungal agent.

Keywords: C18H12S2IBr; L929 cells; LDH; MTT; fluconazole; metabolic activity.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / therapeutic use
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Bromobenzenes / adverse effects*
  • Bromobenzenes / therapeutic use
  • Candida / drug effects
  • Candida / growth & development
  • Candidiasis / drug therapy
  • Cell Line
  • Cell Survival / drug effects
  • Drug Evaluation, Preclinical
  • Drugs, Investigational / adverse effects*
  • Drugs, Investigational / therapeutic use
  • Energy Metabolism / drug effects*
  • Fluconazole / adverse effects
  • Fluconazole / therapeutic use
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins / metabolism
  • Iodobenzenes / adverse effects*
  • Iodobenzenes / therapeutic use
  • Mice
  • Osmolar Concentration
  • Phenyl Ethers / adverse effects*
  • Phenyl Ethers / therapeutic use
  • Repressor Proteins / metabolism
  • Sulfhydryl Compounds / adverse effects*
  • Sulfhydryl Compounds / therapeutic use
  • Survivin

Substances

  • 2,4-dithiophenoxy-1-iodo-4-bromobenzene
  • Antifungal Agents
  • Biomarkers
  • Birc5 protein, mouse
  • Bromobenzenes
  • Drugs, Investigational
  • Inhibitor of Apoptosis Proteins
  • Iodobenzenes
  • Phenyl Ethers
  • Repressor Proteins
  • Sulfhydryl Compounds
  • Survivin
  • Fluconazole