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Diabetes mellitus (DM) is a condition with high blood sugar levels (hyperglycemia), which can have adverse effects on several organ systems. Commercial DM medications are used as therapy for people with DM type II; however, they have side effects that were attributed to high inhibitory effects on α-amylase enzymes. Therefore, new compounds with strong α-glucosidase inhibition and low α-amylase inhibition need to be developed. Cinnamic acid derivatives such as cinnamamides have been shown to possess α-glucosidase inhibitory activity. Bioactive molecules containing a hydrazide moiety, such as isoniazid (INH), are reported to have a broad spectrum of biological activity. Herewith we report the synthesis of a new cinnamamide as a hybridization of trans-cinnamate and INH molecules, namely (E)-N'-(3-(4-bromophenyl)acryloyl)isonicotinohydrazide (5), and its inhibitory activity against α-amylase enzyme. The synthesis of this compound was carried out by the Shiina method, and a yield of 59% was obtained. Cinnamamide 5 has weak α-amylase inhibitory activity than acarbose with IC50 values of 109.8 and 6.37 µM, respectively. [ABSTRACT FROM AUTHOR]

The 3-hydroxy-3-(1H-indol-3-yl)-5-nitrooxindole (3) has been obtained in 88% yield from a reaction of 5-nitroisatin (1) and indole (2) using potassium carbonate as the catalyst. The catalytic reduction of 3 with hydrazine monohydrate and Pd/C catalyst produced 5-amino-3-hydroxy-3-(1H-indol-3-yl)oxindole (4) in 79% yield. The structure of 3 and 4 was justified by FT-IR, 1H/13C NMR, and mass spectroscopies. The cytotoxicity assay of 3 and 4 on HepG2 cells indicated that compound 3 (IC50 0.39 mM) is more active than 4 (IC50 3.56 mM). The molecular docking studies of 3 dan 4 in the binding site of VEGFR2 kinase (PDB ID: 5EW3) showed that the binding energy of compound 3 (-9.1 kcal/mol) was better than that of compound 4 (-8.45 kcal/mol). According to their binding pose, both can be classified as type II kinase inhibitors against VEGFR2 kinase (PDB ID: 5EW3). [ABSTRACT FROM AUTHOR]