Discovery of novel indole derivatives that inhibit NEDDylation and MAPK pathways against gastric cancer MGC803 cells

Bioorg Chem. 2021 Feb:107:104634. doi: 10.1016/j.bioorg.2021.104634. Epub 2021 Jan 8.

Abstract

A series of novel indole derivatives were synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (MGC803, EC-109 and PC-3). Among these analogues, 2-(5-methoxy-1H-indol-1-yl)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (V7) showed the best inhibitory activity against MGC803 cells with an IC50 value of 1.59 μM. Cellular mechanisms elucidated that V7 inhibited colony formation, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, indole analogue V7 inhibited NEDDylation pathway and MAPK pathway against MGC803 cells.

Keywords: Apoptosis; Indole; MAPK pathway; MGC803 cells; NEDDylation pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Damage / drug effects
  • Drug Design
  • Drug Evaluation, Preclinical
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Mitogen-Activated Protein Kinases / metabolism
  • Signal Transduction / drug effects*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Structure-Activity Relationship
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Antineoplastic Agents
  • Indoles
  • Ubiquitin-Conjugating Enzymes
  • Mitogen-Activated Protein Kinases