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.
Yashveer Gautam  1 ,  Sharmistha Das  2 ,  Hamidullah Khan  2 ,  Nandini Pathak  3 ,  Hina Iqbal  1 ,  Pankaj Yadav  1 ,  Vijay Kumar Sirohi  2 ,  Sana Khan  3 ,  Dushyant Singh Raghuvanshi  1 ,  Anila Dwivedi  4 ,  Debabrata Chanda  3 ,  Karuna Shanker  3 ,  Feroz Khan  3 ,  Rituraj Konwar  5 ,  Arvind S Negi  6
Affiliations
  • 1. CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow 226 015, U.P., India.
  • 2. Endocrinology Division, CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow 226031, U.P., India.
  • 3. CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow 226 015, U.P., India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
  • 4. Endocrinology Division, CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow 226031, U.P., India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
  • 5. Endocrinology Division, CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow 226031, U.P., India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India. Electronic address: [email protected].
  • 6. CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow 226 015, U.P., India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India. Electronic address: [email protected].
PMID: 34153643 DOI: 10.1016/j.bmc.2021.116252
Abstract

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.