Synthesis of potent urease inhibitors based on disulfide scaffold and their molecular docking studies.
Disulfide analogs (1-20) have been synthesized, characterized by HR-MS, (1)H NMR and (13)C NMR and screened for urease inhibitory potential. All compounds were found to have varied degree of urease inhibitory potential ranging in between 0.4 ± 0.01 and 18.60 ± 1.24 μM when compared with standard inhibitor thiourea with IC50 19.46 ± 1.20 μM. Structure activity relationship has been established. The binding interactions of compounds with enzyme were confirmed through molecular docking. All the synthesized compounds 1-20 are new. Our compounds are cheaply synthesizable with high yield and can further be studied to discovery lead compounds. We further, tested for carbonic anhydrase, PDE1 and butyrylcholinesterase but they show no activity. On the other hand we evaluated all compounds for cytotoxicity they showed no toxicity.
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia. Electronic address: taha_hej@yahoo.com.
Muhammad
M
Taha
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
Nor Hadiani
NH
Ismail
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
Syahrul
S
Imran
Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
Abdul
A
Wadood
Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan.
Fazal
F
Rahim
Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
Muhammad
M
Riaz
D041721:3T3-L1 Cells; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004220:Disulfides; D004791:Enzyme Inhibitors; D014510:Urease
Cytotoxicity; Disulfide; Molecular docking; Selectivity; Synthesis; Urease inhibition