Synthesis and Cytotoxicity Studies of Br-Substituted Salphen Organic Compounds

Chem Biodivers. 2023 May;20(5):e202200972. doi: 10.1002/cbdv.202200972. Epub 2023 May 4.

Abstract

We present the synthesis and characterization of organic Salphen compounds containing bromine substituents at the para/ortho-para positions, in their symmetric and non-symmetric versions, and describe the X-ray structure and full characterization for the new unsymmetrical varieties. We report for the first time antiproliferative activity in metal-free brominated Salphen compounds, by evaluations in four human cancer cell lines, cervix (HeLa), prostate (PC-3), lung (A549) and colon (LS 180) and one non-cancerous counterpart (ARPE-19). We assessed in vitro cell viability against controls using the MTT assay ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)) and determined the concentration required for 50 % growth inhibition (IC50 ), together with their selectivity vs. non-cancerous cells. We found promising results against prostate (9.6 μM) and colon (13.5 μM) adenocarcinoma cells. We also found a tradeoff between selectivity (up to 3-fold vs. ARPE-19) and inhibition, depending upon the symmetry and bromine-substitution of the molecules, showing up to 20-fold higher selectivity vs. doxorubicin controls.

Keywords: Brominated salphen compounds; Schiff bases; antiproliferative activity; metal-free anti-cancer drugs; selectivity index.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Bromine* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Screening Assays, Antitumor
  • Female
  • HeLa Cells
  • Humans
  • Male
  • Molecular Structure
  • Phenylenediamines / pharmacology
  • Structure-Activity Relationship

Substances

  • salphen
  • Bromine
  • Phenylenediamines
  • Antineoplastic Agents