Design, synthesis and broad spectrum antibreast cancer activity of diarylindoles via induction of apoptosis in aggressive breast cancer cells

Bioorg Med Chem. 2021 Jul 15:42:116252. doi: 10.1016/j.bmc.2021.116252. Epub 2021 Jun 5.


Breast cancer is the second leading cause of cancer deaths in women with significant morbidity and mortality. Present study describes design, synthesis and detailed pharmacology of indole derivatives exhibiting remarkable broad spectrum antiproliferative activity against breast cancer cells. Detailed mechanistic evaluations confirmed induction of G0/G1 arrest, apoptosis induction, loss of mitochondrial integrity, enhanced ROS generation, autophagy, estrogen receptor β-transactivation and increased tubulin polymerization. In in-vivo efficacy studies in rodent model, these indole derivatives induced significant regression in mice mammary tumour on 21 days daily oral dose. Moreover, compounds 19 and 23 were safe in Swiss albino mice in safety studies. These diarylindoles may further be optimized for better efficacy.

Keywords: Acute oral toxicity; Apoptosis; Breast cancer; Diarylindoles; In-vivo efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Polymerization / drug effects
  • Structure-Activity Relationship
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*


  • Antineoplastic Agents
  • Indoles
  • Tubulin
  • Tubulin Modulators