POTENT UREASE INHIBITORS: DESIGN, SYNTHESIS, MOLECULAR DOCKING AND IN-SILICO ADME EVALUATION OF DIHYDROPYRIMIDINE PHTHALIMIDE HYBRIDS | ||||
| Al-Azhar Journal of Pharmaceutical Sciences | ||||
| Article 12, Volume 64, Issue 2, September and October 2021, Page 203-221 PDF (668.69 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/ajps.2021.187826 | ||||
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| Author | ||||
Ahmed Mourad 
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| Pharmacology and Toxicology Department, Faculty of Pharmacy, Port-Said University, Port-Said 42511, Egypt. | ||||
| Abstract | ||||
| Urease inhibition has gained much attention for management of several gastrointestinal and kidney related diseases including peptic ulcer, urolithiasis as well as pyelonephritis. In the current study, novel dihydropyrimidine phthalimide hybrids [WU1] were synthesized and evaluated for their in vitro urease inhibitory activity. The synthesized hybrids were tested their cytotoxic activity. Additionally, the pharmacokinetic properties and drug-likeness were calculated for all synthesized hybrids. Among the synthesized hybrids, compounds 10g, 10e, 10h, 10i, and 10j achieved greater urease inhibitory activity with IC50 range of 12.6 ± 0.1 to 20.1 ± 1.3 µM, compared to the standard urease inhibitor, thiourea with IC50 of 21.0 ± 0.1 µM. Consistent with our findings, the molecular docking study revealed that the most active compounds are docked well with the active sites of urease enzyme. The structure activity relationship concluded that electronic nature, lipophilicity and steric factor of the substituents markedly influenced the urease inhibitory activity. The pharmacokinetic study showed that our compounds have high oral bioavailability, poor blood brain barrier and CNS permeability as well as they have no teratogenic potential. Finally, the synthesized hybrids are considered safe as indicated by the in vitro cytotoxicity assay | ||||
| Keywords | ||||
| Urease inhibitors; Dihydropyrimidine; Phthalimide; Cytotoxicity; Peptic ulcer; Pyelonephritis; Helicobacter pylori | ||||
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