2. Academic Validation
  3. Synthesis of (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-ones as potential cytotoxic agents

Synthesis of (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-ones as potential cytotoxic agents

  • Bioorg Med Chem Lett. 2020 Sep 15;30(18):127432. doi: 10.1016/j.bmcl.2020.127432.
Geeta Sai Mani 1,  Pratibha Anchi 2,  Satish Sunkari 3,  Kavitha Donthiboina 1,  Chandraiah Godugu 4,  Nagula Shankaraiah 5,  Ahmed Kamal 6
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
  • 2 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
  • 3 Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India.
  • 4 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address: chandra.niperhyd@gov.in.
  • 5 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address: shankar@niperhyd.ac.in.
  • 6 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India; Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India; School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 32717368 DOI: 10.1016/j.bmcl.2020.127432
Abstract

The new derivatives based on (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-one scaffold was synthesized and evaluated for their in vitro cytotoxic potential against a panel of Cancer cell lines, viz., A549 (human lung Cancer), HCT-116 (human colorectal Cancer), B16F10 (murine melanoma Cancer), BT-474 (human breast Cancer), and MDA-MB-231 (human triple-negative breast Cancer). Among them, many of the synthesized compounds exhibited promising cytotoxic potential against the panel of tested Cancer cell lines with IC50 <30 µM. Based on the preliminary screening results, the structure-activity relationship (SAR) of the compounds was established. Among the synthesized compounds, 15i displayed a potential anti-proliferative activity against HCT-116 Cancer cell line with an IC50 value of 1.21 ± 0.14 µM. Flow cytometric analysis revealed that compound 15i arrested the G0/G1 phase of the cell cycle. Moreover, increased Reactive Oxygen Species (ROS) generation, clonogenic assay, acridine orange staining, DAPI nuclear staining, measurement of mitochondrial membrane potential (ΔΨm), and annexin V-FITC assays revealed that compound 15i promoted cell death through Apoptosis.

Keywords

Annexin-V; Cell cycle analysis; Cytotoxicity; Imidazo[1,5-a]pyridines; Mitochondrial membrane potential.

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