Design,synthesis, in vitro evaluation,molecular docking and ADME properties studies of hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease |
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| Institution: | 1. Department of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P.O. Box. 1982, Dammam 31441, Saudi Arabia;2. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;3. Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;4. Institute of Advance Research Studies in Chemical Sciences, University of Sindh Jamshoro, Hyderabad 76080, Pakistan;5. Monash University School of Chemical Engineering, 47500 Selangor Alam Campus, Bandar Subway 42300, Malaysia;6. Department of Chemistry, University of Karachi, Karachi 75270, Pakistan;7. Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan;1. Department of Chemistry, Manipal Institute of Technology, Manipal University, India;2. Chemical Sciences & Technology Division (CSTD), CSIR - National Institute for Interdisciplinary Science &Technology (NIIST), India;3. Department of Atomic and Molecular Physics, Manipal University, India;4. Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, India;1. Department of Chemistry, Hazara University, Mansehra 21300, Khyber Pakhtunkhwa, Pakistan;2. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;3. Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan;4. Department of Conservation Sciences, Hazara University, Mansehra 21300, Pakistan;5. Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;6. Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;7. Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia;8. Department of Computer Information Systems, College of Computer Science & Information Technology (CCSIT), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;1. Institute of Chemistry, University of the Punjab, Lahore, 54590, Pakistan;2. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;4. Center of Excellence for Advanced Materials Research (CEAMR), Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;5. Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Islamabad, Pakistan;1. National Demonstration Center for Experimental Chemistry Education, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou, 416000, PR China;2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, PR China;1. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;2. Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Pakistan;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt;2. Department of Microbiology and Immunology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt;3. Developmental Pharmacology Department, National Organization for Drug Control and Research, Giza, Egypt;4. Radioactive Isotopes and Generator Department, Hot Laboratories Center, Egyptian Atomic Energy Authority (EAEA), P.O. Box 13759, Cairo, Egypt;5. Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt |
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| Abstract: | Hybrid bis-coumarin derivatives 1–18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure–activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic. |
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| Keywords: | Biscoumarin Thiadiazole Synthesis Molecular docking Urease inhibition |
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