Synthesis of novel N-(1,3-thiazol-2-yl)benzamide clubbed oxadiazole scaffolds: Urease inhibition, Lipinski rule and molecular docking analyses

Abbasi, Muhammad Athar; Raza, Hussain; Aziz-Ur-Rehman, -; Siddiqui, Sabahat Zahra; Hassan, Mubashir

doi:10.1016/j.bioorg.2018.10.018

Cited by 28 publications

(14 citation statements)

References 24 publications

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“…The metal-containing jack bean urease contains four unique structural domains (Figure 5) [17]. Two nickel atoms coordinate key structural interactions in domain four.…”

Section: Resultsmentioning

confidence: 99%

Symmetrical Heterocyclic Cage Skeleton: Synthesis, Urease Inhibition Activity, Kinetic Mechanistic Insight, and Molecular Docking Analyses

et al. 2019

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The present study focuses on the design and synthesis of a cage-like organic skeleton containing two triazole rings jointed via imine linkage. These molecules can act as urease inhibitors. The in-vitro urease inhibition screening results showed that the combination of the two triazole skeleton in the cage-like morphology exhibited comparable urease inhibition activity to that of the reference thiourea while the metallic complexation, especially with copper, nickel, and palladium, showed excellent activity results with IC50 values of 0.94 ± 0.13, 3.71 ± 0.61, and 7.64 ± 1.21 (3a–c), and 1.20 ± 0.52, 3.93 ± 0.45, and 12.87 ± 2.11 µM (4a–c). However, the rest of compounds among the targeted series exhibited a low to moderate enzyme inhibition potential. To better understand the compounds’ underlying mechanisms of the inhibitory effect (3a and 4a) and their most active metal complexes (3b and 4b), we performed an enzymatic kinetic analysis using the Lineweaver–Burk plot in the presence of different concentrations of inhibitors to represent the non-competitive inhibition nature of the compounds, 3a, 4a, and 4b, while mixed type inhibition was represented by the compound, 3b. Moreover, molecular docking confirmed the binding interactive behavior of 3a within the active site of the target protein.

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“…The metal-containing jack bean urease contains four unique structural domains (Figure 5) [17]. Two nickel atoms coordinate key structural interactions in domain four.…”

Section: Resultsmentioning

confidence: 99%

Symmetrical Heterocyclic Cage Skeleton: Synthesis, Urease Inhibition Activity, Kinetic Mechanistic Insight, and Molecular Docking Analyses

et al. 2019

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“…Topological polar surface area (TPSA) is a term that is frequently used to describe a drug’s ability to penetrate cells. 57 This has proved to be a helpful descriptor in many models and rules for fast estimating various ADME features, particularly biological barrier crossing properties like absorption and brain access. 58 , 59 The TPSA was 89.6 Å2 indicating that TPD can be passively absorbed by the gastrointestinal tract without permeating through the blood-brain barrier.…”

Section: Resultsmentioning

confidence: 99%

“…Topological polar surface area (TPSA) is a term that is frequently used to describe a drug's ability to penetrate cells. 57 This has proved to be a helpful descriptor in many models and rules for fast estimating various ADME For personal use only.…”

Section: Swiss Admementioning

confidence: 99%

Starch Nanoparticles for Enhancement of Oral Bioavailability of a Newly Synthesized Thienopyrimidine Derivative with Anti-Proliferative Activity Against Pancreatic Cancer

Gardouh¹,

El-Din²,

Salem³

et al. 2021

DDDT

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This research aimed to improve water solubility and oral bioavailability of a newly synthesized thienopyrimidine derivative (TPD) with anti-pancreatic cancer activity by loading on starch nanoparticles (SNPs). Methods: TPD was synthesized, purified and its ADME behavior was predicted using Swiss ADME software. A UV spectroscopy method was developed and validated to measure TPD concentration at various dosage forms. SNPs loaded with TPD (SNPs-TPD) were prepared, characterized for particle size, polydispersity index, zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), entrapment efficiency, in-vitro release, and in-vivo animal study. Results: The Swiss ADME results showed that TPD can be administered orally; however, it has low oral bioavailability (0.55) and poor water solubility. The significant regression coefficient of the calibration curve (r 2 = 0.9995), the precision (%RSD < 0.5%) and the accuracy (99.46−101.72%) confirmed the efficacy of the developed UV method. SNPs-TPD had a spherical monodispersed (PDI= 0.12) shape, nanoparticle size (22.98 ± 4.23) and good stability (−21 ± 4.72 mV). Moreover, FT-IR and DSC revealed changes in the physicochemical structure of starch resulting in SNPs formation. The entrapment efficiency was 97% ± 0.45%, and the in-vitro release showed that the SNPs enhanced the solubility of the TPD. The in-vivo animal study and histopathology showed that SNPs enhanced the oral bioavailability of TPD against solid Ehrlich carcinoma. Conclusion: SNPs-TPD were superior in drug solubility and oral bioavailability than those obtained from TPD suspension.

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“…The Lipinski rule of 5 was kept in mind while analysing the results, and the toxicity analysis was done using the online LD50 prediction tool PRO-TOX II (tox-new.charite.de). 33,34,35…”

Section: Drug-likeness Predictionmentioning

confidence: 99%

HRLCMS based metabolite profiling of antioxidant and hypoglycaemic properties of Daruharidra (Berberis aristata): an in vitro and molecular modelling approach

Bhatnagar,

Saini,

Kumari

et al. 2024

New J. Chem.

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Synthesis of novel N-(1,3-thiazol-2-yl)benzamide clubbed oxadiazole scaffolds: Urease inhibition, Lipinski rule and molecular docking analyses

Cited by 28 publications

References 24 publications

Symmetrical Heterocyclic Cage Skeleton: Synthesis, Urease Inhibition Activity, Kinetic Mechanistic Insight, and Molecular Docking Analyses

Symmetrical Heterocyclic Cage Skeleton: Synthesis, Urease Inhibition Activity, Kinetic Mechanistic Insight, and Molecular Docking Analyses

Starch Nanoparticles for Enhancement of Oral Bioavailability of a Newly Synthesized Thienopyrimidine Derivative with Anti-Proliferative Activity Against Pancreatic Cancer

HRLCMS based metabolite profiling of antioxidant and hypoglycaemic properties of Daruharidra (Berberis aristata): an in vitro and molecular modelling approach

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