2. Academic Validation
  3. Design, synthesis, and biological evaluation of chalcone acetamide derivatives against triple negative breast cancer

Design, synthesis, and biological evaluation of chalcone acetamide derivatives against triple negative breast cancer

  • Bioorg Med Chem Lett. 2024 Jul 15:107:129795. doi: 10.1016/j.bmcl.2024.129795.
Puneet Kumar 1,  Ruhi Singh 2,  Deepak Sharma 3,  Qazi Parvaiz Hassan 4,  Boobalan Gopu 5,  Jasha Momo H Anal 6
Affiliations

Affiliations

  • 1 Natural Products and Medicinal Chemistry Division, CSIR - Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 2 Pharmacology Division, CSIR - Indian Institute of Integrative Medicine, Jammu 180001, India.
  • 3 Natural Products and Medicinal Chemistry Division, CSIR - Indian Institute of Integrative Medicine, Jammu 180001, India.
  • 4 Biotechnology Division, CSIR - Indian Institute of Integrative Medicine, Sanatnagar, Srinagar 190005, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 5 Pharmacology Division, CSIR - Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: boobalan.g@iiim.res.in.
  • 6 Natural Products and Medicinal Chemistry Division, CSIR - Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: hmunshel.jasha@iiim.res.in.
PMID: 38750906 DOI: 10.1016/j.bmcl.2024.129795
Abstract

Chalcones are chemical scaffolds found in Natural Products, particularly in Plants, and are considered for structural diversity in medicinal chemistry for drug development. Herein, we designed and synthesised novel acetamide derivatives of chalcone, characterizing them using 1H NMR, 13C NMR, HRMS, and IR spectroscopic methods. These derivatives were then screened against human Cancer cells for cytotoxicity using the SRB assay. Among the tested derivatives, 7g, with a pyrrolidine group, exhibited better cell growth inhibition activity against triple-negative breast Cancer (TNBC) cells. Further assays, including SRB, colony formation, and fluorescent dye-based microscopic analysis, confirmed that 7g significantly inhibited MDA-MB-231 cell proliferation. Furthermore, 7g promoted Apoptosis by upregulating cellular Reactive Oxygen Species (ROS) levels and disrupting mitochondrial membrane potential (MMP). Elevated expression of pro-apoptotic proteins (Bax and Caspase-3) and a higher Bax/Bcl-2 ratio with downregulation of anti-apoptotic (Bcl-2) protein levels were observed in TNBC cells. The above results suggest that 7g can promote cellular death through apoptotic mechanisms in TNBC cells.

Keywords

Acetamide derivatives; Apoptosis; Chalcone; MDA-MB-231; Triple-negative breast cancer.

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