Developing a scaffold for urease inhibition based on benzothiazoles: Synthesis, docking analysis, and therapeutic potential

Abstract

The synthesis, in silico molecular docking, and in vitro urease inhibition studies of a novel series of benzothiazole derivatives are reported. The title compounds in the two series, namely, 2-({5-[(benzothiazol-2-ylthio)methyl]-1,3,4-oxadiazol-2-yl}thio)-1-(4-substitutedphenyl)ethan-1-one and 2-(benzothiazol-2-ylthio)-1-(4-substituted-phenyl)ethan-1-one oxime, were synthesized by the reaction of benzo[d]thiazole-2-thiol with different kinds of intermediates in several steps using both conventional and microwave techniques. All compounds were found to have an excellent degree of ureaseinhibitory potential ranging between 16.16 ± 0.54 and 105.32 ± 2.10 µM when compared with the standard inhibitor acetohydroxamic acid with IC 50 = 320.70 ± 4.24 µM.The structure-activity relationship was established in detail. The binding interactions of the compounds with the enzyme were confirmed through molecular docking.Further, 100 -ns molecular dynamics simulations were performed to investigate the stability and structural perturbations experienced by the most potent compound over the urease active site.

TfOH-Catalyzed Regioselective S–H Insertion of Cyclic Thioamide Derivatives with Diazo Compounds at Room Temperature

“…8c Further transformation of 3r with hydroxylamine led to 73% yield of oxime derivative 5 (Scheme 4c). 14 To gain insights into alkylation process, an isotopic labeling experiment was carried out with the deuterated sulfhydryl benzoxazole 1d-D as the substrate, 15 indicating that proton transfer was achieved from sulfhydryl benzoxazole and TfOH (Scheme 5a). For a comprehensive understanding of reactions, a survey of control experiments was carried out to gain more insights into the catalytic system.…”

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…”

Synthesis and Antimicrobial, Anticancer and Anti-Oxidant Activities of Novel 2,3-Dihydropyrido[2,3-d]pyrimidine-4-one and Pyrrolo[2,1-b][1,3]benzothiazole Derivatives via Microwave-Assisted Synthesis

“…Pyrido [2,3-d]pyrimidine ring systems have assorted biological and pharmacological activities such as being analgesic, anti-inflammatory [1-3], antitubercular [4], antimicrobial [5][6][7], a threonine tyrosine kinase (TTK) inhibitor [8], an adenosine kinase inhibitor [9], antiviral [10], antioxidant [11][12][13][14], a dihydrofolate reductase inhibitor [15,16], and an efficient glucosidase inhibitor [17,18]. Moreover, the 1,3-benzothiazole nucleus is a highly significant scaffold in the drug design, due to important pharmacological and medicinal activities, such as being antiviral [19], antituberculosis [20], an identifier of selective CB2 receptor ligands [21], antitumor [22][23][24], antimicrobial [25][26][27], anticonvulsant [28], a schistosome BCL-2 inhibitor [29], antidiabetic [30], antioxidant [31], an anti-Alzheimer drug [32] and a urease inhibitor [33] among the heterocyclic compounds containing a pyrimidine and benzothiazole nucleus that exhibits biological activity [34][35][36] (Figure 1). kinase (TTK) inhibitor [8], an adenosine kinase inhibitor [9], antiviral [10], antioxidant [11][12][13]…”

“…kinase (TTK) inhibitor [8], an adenosine kinase inhibitor [9], antiviral [10], antioxidant [11][12][13][14], a dihydrofolate reductase inhibitor [15,16], and an efficient glucosidase inhibitor [17,18]. Moreover, the 1,3-benzothiazole nucleus is a highly significant scaffold in the drug design, due to important pharmacological and medicinal activities, such as being antiviral [19], antituberculosis [20], an identifier of selective CB2 receptor ligands [21], antitumor [22][23][24], antimicrobial [25][26][27], anticonvulsant [28], a schistosome BCL-2 inhibitor [29], antidiabetic [30], antioxidant [31], an anti-Alzheimer drug [32] and a urease inhibitor [33] among the heterocyclic compounds containing a pyrimidine and benzothiazole nucleus that exhibits biological activity [34][35][36] (Figure 1). Accordingly, with all of the previous observations of the biological importance and in continuation of our program in the synthesis of pyrido [2,3-d]pyrimidine [37], this study aims to design and develop highly selective and efficacious antimicrobial and anticancer agents of a novel series of pyrido [2,3-d]pyrimidine derivatives bearing different heterocyclic and aryl moieties such as benzothiazole, thiophene, furan, piperonal, naphthalene, and fluorophenyl as a side chain and various aryl derivatives by the microwave irradiation technique.…”