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

Abstract

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 α-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 ¹H NMR,¹³C 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 α-glucosidase and α-amylase enzymes. The biological evaluation revealed the obvious efficiencies of the targeted molecules toward the α-glucosidase enzyme inhibition with the potent IC₅₀ values compared to the standard acarbose. In the case of α-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 μM, respectively. On the other hand, the compound 5f was found to be only promising candidate for α-amylase enzyme but not as effective as the standard acarbose.