Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor |
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| Institution: | 1. Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang, Jiangxi, 330013, China;2. College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China;3. Department of Sports Medicine, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, Jilin, 130021, China;1. State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China;2. The State Key Laboratory of Anti-Infective Drug Development (NO. 2015DQ780357), Sunshine Lake Pharma Co. Ltd, Dongguan 523871, PR China;1. Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282, United States;2. College of Pharmacy, University of Oklahoma Health Science Center, 1110 North Stonewall, Oklahoma City, OK 73117, United States;3. Department of Pharmacology, Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States;4. Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Institutes of Health, 1050 Boyles Street, Frederick, MD 21702, United States;1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Menofia University, Menofia, Egypt;3. Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt;1. Institute for Clinical and Molecular Virology, Friedrich-Alexander University of Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany;2. 4SC AG, Am Klopferspitz 19a, 82152 Planegg-Martinsried, Germany;3. Serology and Virology Division, SEALS Microbiology Prince of Wales Hospital Randwick, School of Women''s and Children''s Health, School of Medical Sciences, School of Biotechnology and Biomolecular Sciences, University of NSW, Sydney, Australia;4. University Grenoble Alpes, CEA, INSERM, BIG-BGE, F-38000 Grenoble, France;1. Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11884, Egypt;3. Faculty of Pharmacy Al-Maareffa University for Science and Technology, Riyadh, Saudi Arabia;4. Zoology Department, Faculty of Science, Al-Azhar University, Cairo 11884, Egypt |
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| Abstract: | A series of pyrrolo2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety were designed, synthesized and evaluated for the anti-proliferative on three cancer cell lines (A549, HepG2 and MCF-7) in vitro. Most of the compounds showed moderate to high potency. Some excellent compounds were tested for the inhibitory activity of c-Met kinase. Compound 34 (c-Met IC50 = 17 nM) was investigated the selectivity against Flt-3, c-Kit, VEGFR-2, ALK, PDGFR-β and RON. Structure-activity relationship studies indicated that hydrogen, fluorine atom, and mono-electron-withdrawing groups (mono-EWGs, such as R2 = F) on R, R1 and R2, respectively, were beneficial for the anti-proliferative activities of the target compounds. Besides, we have took further study on the combined mode between compound 34 and c-Met kinase through molecular docking. |
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| Keywords: | Synthesis Pyrrolo[2 3-b]pyridine derivatives 4-Oxoquinoline Anti-proliferative activity c-Met |
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