3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis,molecular docking and biological evaluation |
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| Institution: | 1. College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China;2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China;1. Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;2. Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia;3. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;4. Faculty of Pharmacy, Universiti Teknologi MARA Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;5. Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad, Pakistan;6. National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 53700, Pakistan;7. Department of Chemistry, Hazara University, Mansehra 21120, Pakistan;8. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan;3. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;4. Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, D-53113 Bonn, Germany;5. Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany;6. Department of Physics, University of Sargodha, Sargodha, Pakistan;1. Department of Chemistry, Art and Science Faculty, Recep Tayyip Erdogan University, Rize, Turkey;2. Department of Chemistry, Faculty of Arts and Sciences, Giresun University, 28049 Giresun, Turkey;1. Department of Chemistry, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan;2. Department of Chemistry, Hazara University, Mansehra, KPK, Pakistan;3. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E. Malaysia;4. Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia;5. Institute of Chemistry, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan;1. Department of Chemistry, Hazara University, Mansehra 21120, Khyber Pukhtankhwa, Pakistan;2. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, KPK, Pakistan;3. Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;4. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), PuncakAlam Campus, 42300 Bandar PuncakAlam, Selangor DarulEhsan, Malaysia;5. Faculty of Applied Science, UiTM, 40450 Shah Alam, Selangor, Malaysia;6. Department of Environmental Science, COMSATS Institute of Information Technology, Abbottabad 22060, KPK, Pakistan;1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, Pakistan;3. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia;4. PCSIR Laboratories Complex, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan |
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| Abstract: | Helicobacter pylori urease is involved in several physiologic responses such as stomach and duodenal ulcers, adenocarcinomas and stomach lymphomas. Thus, inhibition of urease is taken for a good chance to treat H. pylori-caused infections, we have therefore focused our efforts on seeking novel urease inhibitors. Here, a series of arylpropionylhydroxamic acids were synthesized and evaluated for urease inhibition. Out of these compounds, 3-(2-benzyloxy-5-chlorophenyl)-3-hydroxypropionylhydroxamic acid (d24) was the most active inhibitor with IC50 of 0.15 ± 0.05 μM, showing a mixed inhibition with both competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives kinetics parameters of 0.13 and 0.12 μg·mL?1 for Ki and Ki′, respectively. The plasma protein binding assays suggested that d24 exhibited moderate binding to human and rabbit plasma proteins. |
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| Keywords: | 3-Arylpropionylhydroxamic acid Plasma protein binding Kinetics study Non-linear fitting |
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