Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIα inhibitors |
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| Institution: | 1. Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India;2. Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India;3. IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India;4. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad 500 037, India;1. Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan 430079, PR China;2. Xi’an Modern Chemistry Research Institute, Xi’an 710065, PR China;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, India;2. School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi, 110062, India;3. Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne, 3001, Australia;1. Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran;2. Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;3. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran;4. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran;5. Physiology Research Center, Institute of Neuropharmacology, and Department of Toxicology & Pharmacology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran;6. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore;1. Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India;2. Centre for Chemical Biology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India;3. Anti-Cancer Drug Screening Facility (ACDSF), Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India |
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| Abstract: | A series of imidazopyridinyl-1,3,4-oxadiazole conjugates were synthesized and investigated for their cytotoxic activity and some compounds showed promising cytotoxic activity. Compound 8q (NSC: 763639) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10 μM) on all human cancer cell lines. This compound was further evaluated at five dose levels (0.01, 0.1, 1, 10 and 100 μM) to obtain GI50 values ranging from 1.30 to 5.64 μM. Flow cytometric analysis revealed that compound 8q arrests the A549 cells in sub G1 phase followed by induction of apoptosis which was further confirmed by Annexin-V-FITC, Hoechst nuclear staining, caspase 3 activation, measurement of mitochondrial membrane potential and ROS generation. Topo II mediated DNA relaxation assay results showed that conjugate 8q could significantly inhibit the activity of topo II. Moreover, molecular docking studies also indicated binding to the topoisomerase enzyme (PDBID 1ZXN). |
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| Keywords: | Imidazopyridine Oxadiazole Cytotoxicity Topoisomerase Molecular docking |
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