Synthesis and Molecular Docking Studies of Potent Urease Inhibitors Based on Benzoxazole Scaffold

Abstract

In this study, we report the synthesis, in silico molecular docking, and in vitro urease inhibition studies of a novel series of benzoxazole derivatives. The title compound in the series namely (2-(benzo[d]oxazol-2-ylthio)-1-(4-substitute-phenyl) ethan-1-one oxime was synthesized by the reaction of 2aminophenol with different kinds of intermediates in several steps through both conventional and microwave techniques.All compounds were found to have an excellent degree of urease inhibitory potential ranging from 0.46 � 0.01 to 46.10 � 0.45 μM in compared with standard inhibitor acetohydroxamic acid with IC 50 320.70 � 4.24 μM. Structure-activity relationship was established in detail. In addition, we confirmed the binding interactions of compounds with enzymes using molecular docking.

Synthesis, Biological Activity Evaluation, Docking and Molecular Dynamics Studies of New Triazole‐Tetrahydropyrimidinone(thione) Hybrid Scaffolds as Urease Inhibitors

“…Moreover, most previous research studies reported that a bunch of total residues (Ala365, Met366, Ala169, His322, Cys321, Asp223, Asn168) make the hydrophobic and hydrophilic regions and the two embedded Ni 2+ ions conjointly participate a significant role by linking the critical amino acid and ligands. It was been observed that all of the most potent compounds made interaction with them in the active pocket of the urease enzyme [34,36–38] …”

Urease Inhibition and Structure‐Activity Relationship Study of Thiazolidinone‐, Triazole‐, and Benzothiazole‐Based Heterocyclic Derivatives: A Focus Review

“…The inhibitors of the urease can be categorized into two classes; substrate like inhibitors (hydroxyurea, hydroxamic acids) and mechanism based inhibitors (phosphorodiamidates). During the past years, extensive research has been done on the design and development of urease inhibitors such as hydroxamic acids, [51] urea and thiourea derivatives, [52] polyphenols, [53] isoniazids, [54] catechol-based inhibitors, [55] flavonoids, [56] coumarins, [57] indoles, [58] chalcones, [59] thiazoles, [60] thiazolidinones, [61] benzothiazoles, [62] benzoxazoles, [63] benzimidazoles, [64] barbituric acid and thiobarbituric acid derivatives, [65] quinazolinones, [66] triazoles, [67] phosphoramides, [68] sulfonamides, [69] thiadiazoles, [70] oxadiazoles, [71] thiosemicarbazones, [72] diamides, [73] benzenesulfonohydrazides [74] and many more. The most effec-tive inhibitors of urease cited in the literature are phosphorodiamide and phosphorotriamide derivatives such as NBPT (N-n butylthiophosphorictriamide), PPD (phenylphosphorodiamidate), NBPTO (N-n butylphosphorictriamide and flurofamide (Ndiaminophosphoryl-4-fluorobenzamide) [75] (Figure 6).…”

Synthesis of quinazolinone derivatives containing an acyl hydrazone skeleton as potent anti-urease agents enzyme kinetic studies and anti-oxidant properties

“…Jack bean urease inhibitory activity and kinetic studies on the synthesized compounds and thiourea were examined based on previously published studies. 14,[27][28][29][30] Thiourea (Sigma-Aldrich) was used as the standard inhibitor. The urease inhibition percentage was calculated as follows where OD control is the activity of the enzyme without the compound/standard and OD compound is the activity of the enzyme with the compound/standard at different concentrations.…”

“…Jack bean urease inhibitory activity and kinetic studies on the synthesized compounds and thiourea were examined based on previously published studies. 14,27–30 Thiourea (Sigma-Aldrich) was used as the standard inhibitor. The urease inhibition percentage was calculated as follows…”