Synthesis of furo[2,3-c]carbazoles as potent α-glucosidase and α-amylase inhibitors

The carbazole-3-carbaldehyde 2, produced by N-ethyl carbazole via Vilsmeier-Haack reaction, was subjected to Dakin type oxidation with H2O2 and H2SO4 in methanol to produce the carbazole-3-ol 3. The reaction of 3 with a range of commercially available alpha-haloketones 4a-f in the presence of Al2O3 as catalyst in xylene led to their regio-selective cyclization to afford the furo[2,3-c]carbazoles 5a-f. Identification of the furo[2,3-c]carbazoles 5a-f were performed through H-1 NMR,C-13 NMR, FT-IR and high resolution mass spectrometry. Single crystal X-ray diffraction analysis was employed to further confirm the structures of the some of the targeted compounds. In vitro antidiabetic activities of the newly synthesized furocarbazoles 5a-e were investigated utilizing alpha-glucosidase and alpha-amylase enzymes. The biological evaluation revealed the obvious efficiencies of the targeted molecules toward the alpha-glucosidase enzyme inhibition with the potent IC50 values compared to the standard acarbose. In the case of alpha-glucosidase inhibition, the furo[2,3-c]carbazoles chloro substituted 5c and nitro substituted 5f were found to be more potent than acarbose with the values of 215.0 and 162.70 mu M, respectively. On the other hand, the compound 5f was found to be only promising candidate for alpha-amylase enzyme but not as effective as the standard acarbose.