Synthesis,in vitro urease inhibition and molecular docking studies of some novel quinazolin-4(3H)-one derivatives containing triazole,thiadiazole and thiosemicarbazide functionalities |
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| Affiliation: | 1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Dr. Panjwani Centre for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21412, Saudi Arabia;4. PCSIR Laboratories Complex, Karachi, Shahra-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan;5. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, Pakistan;3. Department of Chemistry, COMSATS Institute of Information Technology (CIIT) University Road, Abbottabad 22060, Pakistan;4. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia;5. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan;1. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, 81746-73461, Isfahan, Iran;2. Food and Drug Research Institute, Food and Drug Administration, MOHE, Tehran, Iran;3. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran;4. School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran;5. School of Chemistry, Shahrood University of Technology, Shahrood, Iran;6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;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, 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. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;3. Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, Pakistan;4. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;5. PCSIR Laboratories Com, Karachi, Shahrah-e-Dr. SalimuzzamanSiddiqui, Karachi 75280, Pakistan |
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| Abstract: | A new series of quinazolinone derivatives containing triazole, thiadiazole, thiosemicarbazide functionalities was synthesized and then screened for their in vitro urease inhibition properties. Most of the compounds showed excellent activity with IC50 values ranging between 1.88 ± 0.17 and 6.42 ± 0.23 µg/mL, compared to that of thiourea (IC50 = 15.06 ± 0.68) and acetohydroxamic acid (IC50 = 21.03 ± 0.94), as reference inhibitors. Among the synthesized molecules, compounds 5c, 5e and 5a showed the best inhibitory effect against urease enzyme with IC50 values of 1.88 ± 0.17 µg/mL, 1.90 ± 0.10 and 1.96 ± 0.07 µg/mL, respectively. Moreover in order to give better understanding of the inhibitory activity of synthesized compounds, molecular docking studies were applied at the target sites of jack bean urease enzyme (JBU). Their binding poses and energy calculations were analyzed using induced fit docking (IFD) and prime-MMGBSA tool. Binding poses of studied compounds were determined using induced fit docking (IFD) algorithms. |
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| Keywords: | Triazole Thiadiazole Molecular docking Urease inhibition |
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