Synthesis, Biological Activity and Preliminary in Silico ADMET Screening of Polyamine Conjugates with Bicyclic Systems

Molecules. 2017 May 12;22(5):794. doi: 10.3390/molecules22050794.

Abstract

Polyamine conjugates with bicyclic terminal groups including quinazoline, naphthalene, quinoline, coumarine and indole have been obtained and their cytotoxic activity against PC-3, DU-145 and MCF-7 cell lines was evaluated in vitro. Their antiproliferative potential differed markedly and depended on both their chemical structure and the type of cancer cell line. Noncovalent DNA-binding properties of the most active compounds have been examined using ds-DNA thermal melting studies and topo I activity assay. The promising biological activity, DNA intercalative binding mode and favorable drug-like properties of bis(naphthalene-2-carboxamides) make them a good lead for further development of potential anticancer drugs.

Keywords: DNA binding studies; anticancer activity; in silico ADMET screening; polyamine conjugates.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival
  • DNA / chemistry
  • DNA / metabolism
  • DNA Topoisomerases, Type I / metabolism
  • Drug Design
  • Escherichia coli
  • Humans
  • Indoles / chemistry
  • Naphthalenes / chemistry
  • Nucleic Acid Conformation
  • Polyamines / chemistry*
  • Polyamines / metabolism
  • Polyamines / pharmacology*
  • Quinazolines / chemistry
  • Quinolines / chemistry
  • Rats
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Indoles
  • Naphthalenes
  • Polyamines
  • Quinazolines
  • Quinolines
  • naphthalene
  • indole
  • DNA
  • quinoline
  • DNA Topoisomerases, Type I