A novel five‐step synthetic route to 1,3,4‐oxadiazole derivatives with potent α‐glucosidase inhibitory potential and their in silico studies

Iftikhar, Muhammad Aksam; Shahnawaz,; Saleem, Muhammad; Riaz, Naheed; Aziz-Ur-Rehman, -; Ahmed, Ishtiaq; Rahman, Jameel; Ashraf, Muhammad; Sharif, Muhammad; Khan, Shafi Ullah; Htar, Thet Thet

doi:10.1002/ardp.201900095

Cited by 16 publications

(9 citation statements)

References 34 publications

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“…A Lineweaver–Burk plot was generated to identify the type of inhibition, and the Michaelis–Menten constant (1/V´ max ) value was determined from the plot between reciprocal of the substrate concentration (1/[S]) and reciprocal of enzyme rate (1/V) over various inhibitor concentrations. The experimental inhibitor constant ( K i ) value was constructed by secondary plots of the inhibitor concentration [I] versus 1/Viʹ max [ 15 , 42 , 43 ] .…”

Section: Methodsmentioning

confidence: 99%

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

et al. 2021

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A novel series of phenoxymethybenzoimidazole derivatives ( 9a-n ) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC 50 values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC 50 = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c , 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10310-7.

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Section: Methodsmentioning

confidence: 99%

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

et al. 2021

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“…Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads (Iftikhar et al, 2019). Madiha Kazmi et al has reported three series of diamine-bridged bis-coumarinyl oxadiazole conjugates were designed and synthesized by one-pot multicomponent methodology.…”

Section: Review Of Oxadiazole Derivatives As Potential Antidiabetic A...mentioning

confidence: 99%

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confidence: 99%

overview of oxadiazole-containing compounds as potential antidiabetic agents

Mohammad¹,

Aslam²,

Bavage

et al. 2022

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1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives are amongst the family of heterocycles which showed many promising pharmaceutical applications.Extensive literature survey of 1,3,4-oxadiazole scaffold revealed the activities such as antimicrobial, anti-inflammatory, anti-tubercular, anti-oxidant, anti-cancer, anti-convulsant, anti-diabetic and analgesic properties. 1,2,4-oxadiazole, have shown activity against a variety of diseases like Alzheimer's, parasitic worms (helminths) and other internal parasites, edema, infectious diseases, diabetes, pain and cramp, cardiovascular disease, HIV, tuberculosis, antioxidant, cancer, seizure disorders, and arthritis.As oxadiazoles exhibited many different types of pharmacological activities, we reviewed its pharmacological activities reported by different researchers in the field.In present article we reviewed different articles which has been published in English literature. The search engine used to search for the articles were Scopus, Google scholar, Bentham science, Science direct, Tayler and Francis, Springer nature, Frontiers, and Hindawi. Oxadiazole patent applications have grown by 100% in the previous 9 years, reaching a total of 646, making this a highly sought-after compound in the scientific community. From present review we concluded that Oxadiazoles are potent enough to be developed as potential antidiabetic agents more precisely as DPP-IV inhibitors. We believe that present review can provide insight to the researchers working to develop some novel Oxadiazole derivatives as potential antidiabetic agents.

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“…In this study, we used structure-based virtual screening techniques to investigate the anticancer potential of 14 oxadiazole derivatives which have been reported earlier for their anti-inflammatory activity [ 16 ]. The purpose of the current study was to test the inhibitory potential of 1, 3, 4 oxadiazole derivatives against VEGFR2 for the treatment of renal cancer.…”

Section: Introductionmentioning

confidence: 99%

Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR: Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies

et al. 2022

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Vascular endothelial growth factor (VEGF) is an angiogenic factor involved in tumor growth and metastasis. Gremlin has been proposed as a novel therapeutic pathway for the treatment of renal inflammatory diseases, acting via VEGFR 2 receptor. To date, most FDA-approved tyrosine kinase (TK) inhibitors have been reported as dual inhibitors of EGFR and VEGFR 2. The aim of the present study was to find the potent and selective inhibitor of VEGFR 2 specifically for the treatment of renal cancer. Fourteen previously identified anti-inflammatory compounds i.e., 1, 3, 4 oxadiazoles derivatives by our own group were selected for their anti-cancer potential, targeting the tyrosine kinase (TK) domain of VEGFR2 and EGFR. A detailed virtual screening-based study was designed viz density functional theory (DFT) study to find the compounds’ stability and reactivity, molecular docking for estimating binding affinity, SeeSAR analysis and molecular dynamic simulations to confirm protein ligand complex stability and ADMET properties to find the pharmacokinetic profile of all compounds. The DFT results suggested that among all the derivatives, the 7g, 7j, and 7l were chemically reactive and stable derivatives. The optimized structures obtained from the DFTs were further selected for molecular docking, and the results suggested that 7g, 7j and 7l derivatives as the best inhibitors of VEGFR 2 with binding energy values −46.32, −48.89 and −45.01 kJ/mol. The Estimated inhibition constant (IC50) of hit compound 7j (0.009 µM) and simulation studies of its complexes confirms its high potency and best inhibitor of VEGFR2. All the derivatives were also docked with EGFR, where they showed weak binding energies and poor interactions, important compound 7g, 7j and 7i exhibited binding energy of −31.01, −33.23 and −34.19 kJ/mol respectively. Furthermore, the anticancer potential of the derivatives was confirmed by cell viability (MTT) assay using breast cancer and cervical cancer cell lines. At the end, the results of ADMET studies confirmed these derivatives as drug like candidates. Conclusively, the current study suggested substituted oxadiazoles as the potential anticancer compounds which exhibited more selectivity towards VEGFR2 in comparison to EGFR. Therefore, the identified lead molecules can be used for the synthesis of more potent derivatives of VEGFR2, along with extensive in vitro and in vivo experiments, that can be used to treat various cancers, especially renal cancers, and to prevent angiogenesis due to aberrant expression of VEGFR2.

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A novel five‐step synthetic route to 1,3,4‐oxadiazole derivatives with potent α‐glucosidase inhibitory potential and their in silico studies

Cited by 16 publications

References 34 publications

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

overview of oxadiazole-containing compounds as potential antidiabetic agents

Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR: Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies

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