Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action

Sci Rep. 2019 Apr 23;9(1):6387. doi: 10.1038/s41598-019-42595-y.

Abstract

A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted TP53 tumor suppressor gene. The mechanism of activity was studied according to the p53 status in the cell. Several compounds revealed a good to excellent activity that was similar to or better than the standard anticancer drugs. Some of these appeared to be more active against the p53 null cells than their wild-type counterparts. Intercalating the properties of these compounds could be responsible for their mechanism of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • DNA / metabolism
  • Doxorubicin / pharmacology
  • Drug Design*
  • HCT116 Cells
  • Humans
  • Intercalating Agents / pharmacology
  • Models, Molecular
  • Naphthols / chemical synthesis*
  • Naphthols / chemistry
  • Naphthols / pharmacology*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents
  • Intercalating Agents
  • Naphthols
  • Small Molecule Libraries
  • Tumor Suppressor Protein p53
  • 1-naphthol
  • Doxorubicin
  • DNA
  • calf thymus DNA