A new series of N2-substituted-5-(p-toluenesulfonylamino)phthalimide analogues as α-glucosidase inhibitors

Bian, Xiaoli; Wang, Qian; Ke, Changhu; Zhao, Guilan; Li, Yiping

doi:10.1016/j.bmcl.2013.02.011

Cited by 18 publications

(6 citation statements)

References 22 publications

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“…Phthalimide scaffold also was applied in the design of several series of the synthetic α-glucosidase inhibitors 18 – 20 . On the other hand, one of the other pharmacophores that in the design of new potent α-glucosidase inhibitors was applied is benzenesulfonamide 19 , 21 . Therefore, in continuation of our ongoing research on introducing new hybrid compounds with significant inhibitory activity against α-glucosidase, herein, we designed and synthesized a new series of phthalimide-benzenesulfonamide hybrids 4a – n .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, in vitro α-glucosidase inhibition, docking, and molecular dynamics of new phthalimide-benzenesulfonamide hybrids for targeting type 2 diabetes

Askarzadeh

Azizian

Adib

et al. 2022

Sci Rep

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In the present work, a new series of 14 novel phthalimide-benzenesulfonamide derivatives 4a–n were synthesized, and their inhibitory activity against yeast α-glucosidase was screened. The obtained results indicated that most of the newly synthesized compounds showed prominent inhibitory activity against α-glucosidase. Among them, 4-phenylpiperazin derivative 4m exhibited the strongest inhibition with the IC50 value of 52.2 ± 0.1 µM. Enzyme kinetic study of compound 4m proved that its inhibition mode was competitive and Ki value of this compound was calculated to be 52.7 µM. In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the target compounds over the active site of α-glucosidase. Obtained date of these studies demonstrated that our new compounds interacted as well with the α-glucosidase active site with the acceptable binding energies. Furthermore, in silico druglikeness/ADME/Toxicity studies of compound 4m were performed and predicted that this compound is druglikeness and has good ADME and toxicity profiles.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, in vitro α-glucosidase inhibition, docking, and molecular dynamics of new phthalimide-benzenesulfonamide hybrids for targeting type 2 diabetes

Askarzadeh

Azizian

Adib

et al. 2022

Sci Rep

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“…Therefore, there is considerable interest in the design and synthesis of non-saccharide AGIs. [16][17][18][19][20][21] Bharatham et al investigated the binding mode of interaction of several sugar/non-saccharide AGIs at the active site of α-glucosidase and developed a pharmacophore model, which represened the critical features responsible for α-glucosidase inhibitory activity. 17) In our previous study, we found that several phthalimide derivatives exhibited good α-glucosidase inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants

Jian-gang

Chen

et al. 2019

Biological & Pharmaceutical Bulletin

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In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC 50 values of 0.15 0.01, 0.086 0.01 and 0.32 0.02 mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-αglucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.

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“…Bian and coworkers screened, against α-glucosidase, a series of N -substituted-( p -toluenesulfonylamino)phthalimides. Many analogues provide good inhibitions of the enzymes, with aromatic pendants and tethers containing 1–3 atoms generally producing the most potent inhibitions [ 3 ].…”

Section: Glycosidase Assaymentioning

confidence: 99%

“…Phthalimide analogues have also been shown to display glycosidase inhibition [ 3 , 4 , 5 ], with the 2,3,4,5-tetrachlorophthalimide scaffold deemed necessary for potent activity and the corresponding unsubstituted phthalimide derivatives showing reduced activity [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Borylated 2,3,4,5-Tetrachlorophthalimide and Their 2,3,4,5-Tetrachlorobenzamide Analogues: Synthesis, Their Glycosidase Inhibition and Anticancer Properties in View to Boron Neutron Capture Therapy

et al. 2022

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Tetrachlorinated phthalimide analogues bearing a boron-pinacolate ester group were synthesised via two synthetic routes and evaluated in their glycosidase modulating and anticancer properties, with a view to use them in boron neutron capture therapy (BNCT), a promising radiation type for cancer, as this therapy does little damage to biological tissue. An unexpected decarbonylation/decarboxylation to five 2,3,4,5-tetrachlorobenzamides was observed and confirmed by X-ray crystallography studies, thus, giving access to a family of borylated 2,3,4,5-tetrachlorobenzamides. Biological evaluation showed the benzamide drugs to possess good to weak potencies (74.7–870 μM) in the inhibition of glycosidases, and to have good to moderate selectivity in the inhibition of a panel of 18 glycosidases. Furthermore, in the inhibition of selected glycosidases, there is a core subset of three animal glycosidases, which is always inhibited (rat intestinal maltase α-glucosidase, bovine liver β-glucosidase and β-galactosidase). This could indicate the involvement of the boron atom in the binding. These glycosidases are targeted for the management of diabetes, viral infections (via a broad-spectrum approach) and lysosomal storage disorders. Assays against cancer cell lines revealed potency in growth inhibition for three molecules, and selectivity for one of these molecules, with the growth of the normal cell line MCF10A not being affected by this compound. One of these molecules showed both potency and selectivity; thus, it is a candidate for further study in this area. This paper provides numerous novel aspects, including expedited access to borylated 2,3,4,5-tetrachlorophthalimides and to 2,3,4,5-tetrachlorobenzamides. The latter constitutes a novel family of glycosidase modulating drugs. Furthermore, a greener synthetic access to such structures is described.

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A new series of N2-substituted-5-(p-toluenesulfonylamino)phthalimide analogues as α-glucosidase inhibitors

Cited by 18 publications

References 22 publications

Design, synthesis, in vitro α-glucosidase inhibition, docking, and molecular dynamics of new phthalimide-benzenesulfonamide hybrids for targeting type 2 diabetes

Design, synthesis, in vitro α-glucosidase inhibition, docking, and molecular dynamics of new phthalimide-benzenesulfonamide hybrids for targeting type 2 diabetes

A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants

Borylated 2,3,4,5-Tetrachlorophthalimide and Their 2,3,4,5-Tetrachlorobenzamide Analogues: Synthesis, Their Glycosidase Inhibition and Anticancer Properties in View to Boron Neutron Capture Therapy

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