Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies. Issue 38 (9th October 2020)

• Record Type: Journal Article
• Authors: Chaudhry, Faryal; Naureen, Sadia; Aslam, Misbah; Al‐Rashida, Mariya; Rahman, Jameel; Huma, Rahila; Fatima, Javeria; Khan, Mavra; Munawar, Munawar Ali; Ain Khan, Misbahul
• Is Part Of: ChemistrySelect. Volume 5:Issue 38(2020)
• Page Start: 11817
• Page End: 11821
• Publication Date: 2020-10-09
• Subjects: Enzymes -- Imidazole -- Inhibitors -- Molecular docking -- Pyrazole; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202002482
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Towards discovery of effective urease inhibitors; we disclose here a hybrid series of imidazole and pyrazole motifs as potent antiurease agents. A para ‐toluenesulfonic acid (TsOH) catalyzed, facile synthetic approach was employed for the preparation of targeted molecular designs in good yields upto 94 %. The novel scaffolds were characterized by different spectroscopic means (FTIR, NMR, and Mass spectrometry) and elemental analysis helped to identify the purity of these compounds. Afterwards, the derivatives was tested against Jack bean's urease enzyme to explore their inhibiting potencies. All analogues (4 a ‐4 l ) were found active against the studied enzyme in comparison with the standard drug thiourea (IC50= 21.26±0.12 μM). However, following dibromo substituted derivatives: 4 f, 4 g, 4 h, 4 i, 4 j, 4 k, and 4 l were surfaced out as potent urease inhibitors among the series. The identified lead candidates were meta ‐nitro substituted 4 k with IC50= 0.7±0.002 μM and a para ‐nitro containing compound 4 l with IC50= 1.0±0.003 μM. As observed in docking calculations, ionic and hydrogen bonding, π ‐stacking, interaction with nickel ions and other hydrophobic interactions probably stabilized the ligand bindings at the active site of urease. Abstract : This research was aimed to prepare a series of imidazole‐pyrazole conjugates and evaluate these scaffolds for their inhibiting potentials against urease enzyme. Two most promising urease inhibitors of the series were nitro substituted compounds 4 k and 4 l. This explorative study involved preliminary biological in‐vitro evaluation of the synthesized compounds and in silico molecular docking calculations which facilitated in indentifying new potent core structures that could lead to better anti‐urease drug candidates.