Assessment of Immunomodulatory Activities and in vitro Toxicity of New Quinolone 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate

Immunol Invest. 2017 May;46(4):341-360. doi: 10.1080/08820139.2017.1280050. Epub 2017 Mar 13.

Abstract

Our previous studies on leukemia cells L1210 and cervical cancer HeLa cells revealed cytotoxic effects of the 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate (E2h), a new synthetically prepared quinolone derivative, toward selected cancer cell lines. The aim of the present study was to examine the cytotoxicity of E2h toward next cell lines and tissues; that is, human cancer HL-60 and A549 cells, human non-cancer fibroblast BHNF-1 cells, and reconstructed human epidermis tissues. Further we investigated the immunomodulatory activity of E2h on murine macrophage RAW 264.7 cells. Selenadiazoloquinolone E2h induced specific antiproliferative/cytotoxic activity against leukemia HL-60 cells and is the potent inducer of apoptotic cell death. Quinolone derivative demonstrated the immunomodulatory activities on RAW 264.7 cell line murine macrophages. The immunobiological studies revealed time- and concentration-dependent effective immunomodulation of pro- and anti-inflammatory cytokines' release and antiproliferative/cytotoxic effect following exposure of RAW 264.7 cells to E2h.

Abbreviations: DMEM, Dulbecco's modified eagle medium; DMSO, Dimethylsulfoxide; EtBr, Ethidium bromide; PI, Propidium iodide; E2h, 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate.

Keywords: Anticancer; HL-60; apoptosis; cytokines; cytotoxicity; immunomodulation; proliferation; quinolones.

MeSH terms

  • A549 Cells
  • Adenocarcinoma / drug therapy*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Growth Processes / drug effects
  • Fibroblasts / drug effects*
  • Fibroblasts / pathology
  • HL-60 Cells
  • Humans
  • Immunomodulation
  • Leukemia / drug therapy*
  • Macrophages / drug effects*
  • Macrophages / pathology
  • Mice
  • Organoselenium Compounds / chemical synthesis
  • Organoselenium Compounds / pharmacology*
  • Quinolones / chemical synthesis
  • Quinolones / pharmacology*
  • RAW 264.7 Cells

Substances

  • 7-ethyl 9-ethyl-6-oxo-6,9-dihydro(1,2,5)selenadiazolo(3,4-h)quinoline-7-carboxylate
  • Antineoplastic Agents
  • Organoselenium Compounds
  • Quinolones