Design and synthesis of novel imidazo[4,5-b]pyridine based compounds as potent anticancer agents with CDK9 inhibitory activity |
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| Institution: | 1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt;2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;3. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;1. Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;2. Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China;1. Department of Chemistry, Nehru Arts and Science College, Kannur University, Kannur, India;2. Post Graduate and Research Department of Chemistry, Jamal Mohamed College, Bharathidasan University, Tiruchirapalli, India;3. Department of Biosciences and Bioengineering, IIT Mumbai, India;4. Post Graduate and Research Department of Chemistry, Kasargod Govt. College, Kannur University, Kasaragod, India;5. Research Center, Department of Chemistry, East West Institute of Technology, Bangalore, India;6. Department of P.G. Studies and Research in Industrial Chemistry, Kuvempu University, Jnana Sahyadri, Shankaraghatta, Shimoga, Karnataka, India;7. School of Chemical Sciences, Kannur University, Payyanur Campus, Edat P.O. Kannur, Kerala, India;8. Central University of Kerala, Vidyanagar, Kasaragod, Periya, Kerala, India;1. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China;2. Shanghai Bone Tumor Institution, Shanghai, 201620, China;3. Department of Orthopedics, RWTH Aachen University Clinic, Pauwelsstraße 30, 52074, Aachen, Germany;1. Medicinal Chemistry and Pharmacology Division, CSIR – Indian Institute of Chemical Technology, Hyderabad 500007, India;2. Academy of Scientific and Innovative Research (AcSIR), CSIR – Indian Institute of Chemical Technology, Hyderabad 500007, India;3. School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India;4. Department of Crop Protection Chemicals, CSIR – Indian Institute of Chemical Technology, Hyderabad 500007, India;1. Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India;2. Centre for Interdisciplinary Research in Basic Science, Jamia Nagar, 110 025, New Delhi, India;3. Grupo Xenomar, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Química, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071, A Coruña, Spain;1. Division of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, Athens 15771, Greece;2. Molecular Virology Laboratory, Hellenic Pasteur Institute, 127 Vas. Sofias ave., 11521 Athens, Greece |
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| Abstract: | New imidazo4,5-b]pyridine derivatives were designed, synthesized and screened for their anticancer activity against breast (MCF-7) and colon (HCT116) cancer cell lines. Nine compounds (I, II, IIIa, IIIb, IV, VI, VIIa, VIII, IX) showed significant activity against MCF-7, while six compounds (I, VIIc, VIIe, VIIf, VIII, IX) elicited a remarkable activity against HCT116. Compounds showing significant anticancer activity revealed remarkable CDK9 inhibitory potential (IC50 = 0.63–1.32 μM) relative to sorafenib (IC50 = 0.76 μM). Moreover, a molecular docking study was performed to illustrate the binding mode of the most active compounds in the active site of CDK9 where it revealed superior binding affinity relative to the natural ligand (T3C). |
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| Keywords: | Anticancer CDK9 HCT116 MCF-7 |
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