Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies
Faryal Chaudhry, Sadia Naureen, Misbah Aslam, Mariya al‐Rashida, Jameel Rahman, Rahila Huma, Javeria Fatima, Mavra Khan, Munawar Ali Munawar, Misbahul Ain Khan
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 (IC 50= 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 IC 50= 0.7±0.002 μM and a para ‐nitro containing compound 4 l with IC 50= 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.