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

• Main Authors: Mezna Saleh Altowyan, Assem Barakat, Abdullah Mohammed Al-Majid, H.A. Al-Ghulikah
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: Molecules
• Subjects: spiroindolone; antidiabetic; hypoglycemic; α-amylase; α-glucosidase
• Online Access: https://www.mdpi.com/1420-3049/24/12/2342

Inhibition of &#945;-amylase and &#945;-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 (compounds <b>2a&#8722;f</b>), with a substituted isatin (compounds <b>3a&#8722;c</b>) and heterocyclic amino acids (compounds <b>4a,b</b>). The target spiroindolone analogues <b>5a&#8722;r</b> were evaluated for their potential inhibitory activities against the enzymes &#945;-amylase and &#945;-glucosidase. Preliminary results indicated that some of the target compounds exhibit promising &#945;-amylase and &#945;-glucosidase inhibitory activity. Among the tested spiroindolone analogues, the cycloadduct <b>5r</b> was found to be the most active (IC₅₀ = 22.61 &#177; 0.54 &#956;M and 14.05 &#177; 1.03 &#956;M) as &#945;-amylase and &#945;-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.