Synthesis of (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-ones as potential cytotoxic agents |
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| Institution: | 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. School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;1. Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, C.P. 04510, Cd. México, Mexico;2. Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, C.P. 04510, Cd. México, Mexico;1. Drug Discovery Research, Astellas Pharma Inc.; 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan;1. Department of Environment Engineering Chemistry, Luoyang Institute of Science Technology, Luoyang 471023, PR China;2. College of Chemistry and Chemical Engineering, Henan Key Laboratory of Fuction-Oriented Porous Materials, Luoyang Normal University, Luoyang 471022, PR China;1. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, China;2. Department of Chemistry, Xiamen University, Xiamen, 361005, China |
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| Abstract: | The new derivatives based on (Z)-3-(arylamino)-1-(3-phenylimidazo1,5-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. |
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| Keywords: | Cytotoxicity Cell cycle analysis Annexin-V Mitochondrial membrane potential |
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