Synthesis and cellular effects of novel 1,3,5-triazine derivatives in DLD and Ht-29 human colon cancer cell lines

Invest New Drugs. 2020 Aug;38(4):990-1002. doi: 10.1007/s10637-019-00838-9. Epub 2019 Sep 13.


This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.

Keywords: Apoptosis; Colon cancer; Drug design; Hybrid anticancer drugs; Nitrogen mustards; Triazine derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Triazines / chemical synthesis
  • Triazines / pharmacology*


  • Antineoplastic Agents
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Triazines