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.
- 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: [email protected].
- 5. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address: [email protected].
- 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: [email protected].
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.