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Design,Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors |
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| Authors: | Sadaf Mutahir Muhammad Asim Khan Abdulrahman Abdulaziz Almehizia Amr Salah Abouzied Nasrin Eldirdiri Khalifa Ahmed Mohamed Naglah Haishan Deng Moamen Salaheldeen Refat Weam Mohamed Ali Khojali Bader Huwaimel |
| Affiliation: | 1. School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276000 China;2. Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451 Saudi Arabia;3. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442 Saudi Arabia Department of Pharmaceutical Chemistry, National Organization for Drug Control and Research (NODCAR), Giza, 12553 Egypt;4. Department of pharmaceutics, College of Pharmacy, University of Hail, Hail, 81442 Saudi Arabia Department of pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum, 11115 Sudan;5. School of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, 210094 China;6. Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif, 21944 Saudi Arabia;7. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442 Saudi Arabia Department of pharmaceutical chemistry, faculty of pharmacy, Omdurman Islamic University, Omdurman, 14415 Sudan;8. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442 Saudi Arabia Medical and Diagnostic Research Center, University of Hail, Hail, 81442 Saudi Arabia |
| Abstract: | Mannich bases consisting of 1,3,4-oxadiazole-2-thione ( 3 a – 3 l ) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4-chlorophenyl (−R) and 4-hydroxyphenyl (−R′) was most active with IC50 9.45±0.05 μM followed by 3 e (IC50 22.52±0.15 μM) in which −R was phenyl and −R′ was isopropyl group. However, when both −R and −R′ were either 4-chlorophenyl groups ( 3 l ) or only −R′ was 4-nitrophenyl ( 3 i ), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts. |
| Keywords: | Mannich bases 1,3,4-oxadiazole-2-thione urease inhibitors molecular docking |