Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches

Hussain, Rafaqat; Rehman, Wajid; Khan, Shoaib; Taha, Muhammad; Khan, Yousaf; Sardar, Asma; Khan, Imran; Shah, Syed Adnan Alı

doi:10.1016/j.molstruc.2023.136185

Cited by 31 publications

(2 citation statements)

References 30 publications

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“…As a result of using a variety of software tools, we were able to visualize the interaction between ligands and amino acids, determining their distances and interaction types, such as C-H bonds, pi-R interactions, pi-S interactions, hydrogen bonds, pi-pi T-shaped interactions, pi-stacking, and pi-sigma interactions, which are shown below in Figures 2-12 and Table 2. Our research team synthesized various heterocyclic compounds with a variety of substitutions and evaluated their potential biological activity using diverse molecular docking software [48][49][50][51][52][53].…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

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The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline–Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents

Khan,

Hussain

et al. 2023

Pharmaceuticals

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In the present work, a concise library of benzothiazole-derived pyrazoline-based thiazole (1–17) was designed and synthesized by employing a multistep reaction strategy. The newly synthesized compounds were screened for their α-glucosidase and urease inhibitory activities. The scaffolds (1–17) were characterized using a combination of several spectroscopic techniques, including FT-IR, 1H-NMR, 13C-NMR, and EI-MS. The majority of the synthesized compounds demonstrated a notable potency against α-glucosidase and urease enzymes. These analogues disclosed varying degrees of α-glucosidase and urease inhibitory activities, with their IC50 values ranging from 2.50 to 17.50 μM (α-glucosidase) and 14.30 to 41.50 (urease). Compounds 6, 7, 14, and 12, with IC50 values of 2.50, 3.20, 3.40, and 3.50 μM as compared to standard acarbose (IC50 = 5.30 µM), while the same compounds showed 14.30, 19.20, 21.80, and 22.30 comparable with thiourea (IC50 = 31.40 μM), respectively, showed excellent inhibitory activity. The structure−activity relationship revealed that the size and electron-donating or electron-withdrawing effects of substituents influenced the enzymatic activities such as α-glucosidase and urease. Compound 6 was a dual potent inhibitor against α-glucosidase and urease due to the presence of -CF3 electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of α-glucosidase and urease with minimum IC50 values. Moreover, in silico studies on most active compounds, i.e., 6, 7, 14, and 12, were also performed to understand the binding interaction of most active compounds with active sites of α-glucosidase and urease enzymes.

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Section: Molecular Docking Studiesmentioning

confidence: 99%

“…The positive control used was acarbose solution. A percentage of the inhibitory activity was calculated using a control sample without the inhibitors [53].…”

Section: α-Glucosidase Inhibitory Assaymentioning

confidence: 99%

The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline–Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents

Khan,

Hussain

et al. 2023

Pharmaceuticals

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Novel Thiadiazole Derivatives as Potential Anti‐Alzheimer Agent: Synthesis, Activity of Molecular Interactions and their in Silico Assessment

Du,

Lan,

Guo

et al. 2024

ChemistrySelect

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A series of thiadiazole derivatives were designed and synthesized as dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) for the treatment of Alzheimer's disease (AD). Furthermore, the compounds were assayed for their inhibitory activity to AChE and BuChE in vitro, and the results indicated that most of the compounds had moderate inhibitory activity to AChE and BuChE. Among them, compound 11 u showed the best inhibitory activity against AChE and BuChE (eeAChE, IC50=2.73 μM; eqBuChE, IC50=0.65 μM), which showed approximately 2‐fold more activity against AChE enzyme than galantamine and approximately 28‐fold more activity against BuChE enzyme than galantamine. In addition, molecular docking studies have shown that compound 11 u could bind to the catalytic active site (CAS) and peripheral anion site (PAS) of AChE and BuChE. Among them, compound 11 u combined with BuChE and exhibited a mixed inhibition pattern consistent with enzyme kinetics studies. The interaction's stability of 11 u‐AChE/BuChE were also assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound 11 u in the cavity of the AChE/BuChE. Moreover, the molecular properties of all compounds were predicted by online through the SwissADME, and the best active compound 11 u matched the properties of most orally administered drugs. All these suggested that 11 u could be considered as a lead compound for the development of drugs for AD.

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Novel 3,5‐Dimethylpyrazole‐Linked 1,2,4‐Triazole‐3‐thiols as Potent Antihyperglycemic Agents: Synthesis, Biological Evaluation, and In Silico Molecular Modelling Investigations

Rouzi,

Mortada,

Hassan

et al. 2024

ChemistrySelect

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In this work, a series of pyrazole‐linked 1,2,4‐triazole‐3‐thiol derivatives (3a–i) were prepared and identified by 13C NMR, 1H NMR, and mass spectrometry (ESI‐MS) data. The newly synthesized molecules were also evaluated in vitro for their α‐amylase and α‐glucosidase inhibitory potential. All newly synthesized compounds exhibited potent α‐glucosidase inhibition activity with IC50 in the range of 1.016 ± 0.70 to 24.40 ± 0.02 µM and good α‐amylase inhibitory with IC50 in the range of 49.91 ± 0.32 to 500 µM, as compared to acarbose. The most potent compound among this series is derivative 3e, with IC50 value of 1.016 ± 0.70 µM, which is many folds more than that of acarbose. In addition, in docking studies, both compounds exhibited good interactions at the active region of target proteins. Therefore, this study may lead via structural modifications to the discovery of new potent α‐amylase and α‐glucosidase inhibitors useful in the diabetes treatment.

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Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches

Cited by 31 publications

References 30 publications

The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline–Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents

The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline–Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents

Novel Thiadiazole Derivatives as Potential Anti‐Alzheimer Agent: Synthesis, Activity of Molecular Interactions and their in Silico Assessment

Novel 3,5‐Dimethylpyrazole‐Linked 1,2,4‐Triazole‐3‐thiols as Potent Antihyperglycemic Agents: Synthesis, Biological Evaluation, and In Silico Molecular Modelling Investigations

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