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Spiroindolone Analogues as Potential Hypoglycemic with Dual Inhibitory Activity on ?-Amylase and ?-Glucosidase.

ABSTRACT: Inhibition of ?-amylase and ?-glucosidase by specified synthetic compounds during the digestion of starch helps control post-prandial hyperglycemia and could represent a potential therapy for type II diabetes mellitus. A new series of spiroheterocyclic compounds bearing oxindole/benzofuran/pyrrolidine/thiazolidine motifs were synthesized via a 1,3-dipolar cyclo-addition reaction approach. The specific compounds were obtained by reactions of chalcones having a benzo[b]furan scaffold (compounds 2a-f), with a substituted isatin (compounds 3a-c) and heterocyclic amino acids (compounds 4a,b). The target spiroindolone analogues 5a-r were evaluated for their potential inhibitory activities against the enzymes ?-amylase and ?-glucosidase. Preliminary results indicated that some of the target compounds exhibit promising ?-amylase and ?-glucosidase inhibitory activity. Among the tested spiroindolone analogues, the cycloadduct 5r was found to be the most active (IC50 = 22.61 ± 0.54 ?M and 14.05 ± 1.03 ?M) as ?-amylase and ?-glucosidase inhibitors, with selectivity indexes of 0.62 and 1.60, respectively. Docking studies were carried out to confirm the binding interaction between the enzyme active site and the spiroindolone analogues.

SUBMITTER: Altowyan MS

PROVIDER: S-EPMC6630796 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Spiroindolone Analogues as Potential Hypoglycemic with Dual Inhibitory Activity on α-Amylase and α-Glucosidase.

Altowyan Mezna Saleh MS Barakat Assem A Al-Majid Abdullah Mohammed AM Al-Ghulikah H A HA

Molecules (Basel, Switzerland) 20190625 12

Inhibition of α-amylase and α-glucosidase by specified synthetic compounds during the digestion of starch helps control post-prandial hyperglycemia and could represent a potential therapy for type II diabetes mellitus. A new series of spiroheterocyclic compounds bearing oxindole/benzofuran/pyrrolidine/thiazolidine motifs were synthesized via a 1,3-dipolar cyclo-addition reaction approach. The specific compounds were obtained by reactions of chalcones having a benzo[<i>b</i>]furan scaffold (compo ...[more]

PMID: 31242688

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Spiroindolone Analogues as Potential Hypoglycemic with Dual Inhibitory Activity on ?-Amylase and ?-Glucosidase.

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Spiroindolone Analogues as Potential Hypoglycemic with Dual Inhibitory Activity on α-Amylase and α-Glucosidase.

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