Synthesis and biological evaluation of 2,4,6-trinitroaniline derivatives as potent antitumor agents

Hacıoğlu N., Güngör T., Tokay E., Önder F., Ay M., Köçkar F.

Monatshefte fur Chemie, vol.151, no.10, pp.1629-1641, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 151 Issue: 10
  • Publication Date: 2020
  • Doi Number: 10.1007/s00706-020-02690-7
  • Journal Name: Monatshefte fur Chemie
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1629-1641
  • Keywords: Cytotoxicity, Trinitroaniline, Synthesis, Nitro compound, Apoptosis, Hepatocellular carcinoma
  • Çanakkale Onsekiz Mart University Affiliated: Yes


© 2020, Springer-Verlag GmbH Austria, part of Springer Nature.Abstract: Nitro group-containing compounds are well known as effective anticancer drugs. The aim of the study is to synthesize a series of trinitroaniline derivatives to determine their potential antitumor activities on diverse cancer cell models, anti-apoptotic and anti-metastatic features on hepatoma cells. The anti-proliferative studies show that IC50 values of N-phenyl-2,4,6-trinitroaniline, N-(2,4,6-trinitrophenyl)naphthalen-1-amine, N-(2,4,6-trinitrophenyl)naphthalen-2-amine, N-(3-nitrophenyl)-2,4,6-trinitroaniline were similar to IC50 value of cisplatin in Hep3B cells. In fact, IC50 value of N-(3,5-difluorophenyl)-2,4,6-trinitroaniline is better than cisplatin. In addition, all compounds could decrease the expression of the cell cycle checkpoint protein cyclin D1. To investigate the effect of compounds on the apoptotic pathway, mRNA and protein expressions of Bcl-2 and Bax were analyzed with qRT-PCR and Western blot. Annexin V staining assay, apoptotic mRNA and protein analysis indicate that N-isopropyl-2,4,6-trinitroaniline, N-(2,4,6-trinitrophenyl)-5-methylisoxazole-3-amine, N-(3-nitrophenyl)-2,4,6-trinitroaniline, N-(4-nitrophenyl)-2,4,6-trinitroaniline induce intrinsic apoptosis by increasing the ratio of Bax/Bcl-2 expression. In addition, colony formation and wound healing assays confirmed that these compounds also inhibit the metastatic activity of Hep3B cells. 2,4,6-Trinitroaniline derivatives, especially N-(3-nitrophenyl)-2,4,6-trinitroaniline might be used as candidate for the development of new antitumor drugs. Graphic abstract: [Figure not available: see fulltext.].