PMA-SiO2 catalyzed synthesis of indolo[2,3-c]quinolines as potent anti cancer agents

Bioorg Med Chem Lett. 2015 Jun 1;25(11):2360-5. doi: 10.1016/j.bmcl.2015.04.018. Epub 2015 Apr 18.

Abstract

PMA-SiO2 catalyzed Pictet-Spengler reaction of aryl amine linked to C-3 of the indole and the aryl aldehydes was achieved. In the series of the synthesized compounds, 6b, 10b and 12b were found to be cytotoxic against prostate, lung, breast and cervical cancer cell lines selectively with no significant effect on the growth of the control fibroblast cell line NIH3T3. Further determining their cytotoxic potential we found that 10b and 12b show cell cycle arrest in DU145 prostate cancer cells indicating a role in cell cycle progression. Both the molecules showed effect on decreased phosphorylation of NF-κB on serine 536 residue which is strongly implicated in many different types of cancers. Taken together, the series of indoloquinolines elicit potent anti-cancer potential providing a mean for developing novel indoloquinoline based anti-cancer agents.

Keywords: Anti cancer; Bronsted acid; Carboline; Indoloquinoline; Pictet–Spengler.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemistry
  • Polymethacrylic Acids / chemistry*
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Silicon Dioxide / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Polymethacrylic Acids
  • Quinolines
  • poly(MPC-co-MA)
  • Phosphorylcholine
  • Silicon Dioxide