Synthesis and profiling (in vitro and in silico) of the 6-methoxy/hydroxy substituted 7-acetyl-2-aryl-5-bromobenzofurans for antihyperglycemic, cytotoxic and antioxidant properties

Abstract

A small library of the 7-acetyl-2-aryl-5-bromo-6-methoxybenzo[b]furans 2a–f was synthesized and transformed into the corresponding ortho-(hydroxyacetyl) substituted 2-arylbenzo[b]furan derivatives 3a–f. The structures of both series of compounds were characterized using a combination of spectroscopic techniques complemented with single crystal X-ray diffraction (XRD) analysis of a representative example from each category. Both series of compounds were evaluated through enzymatic assays in vitro for potential to inhibit α-glucosidase, α-amylase and/or protein tyrosine phosphatase 1 beta (PTP1B) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The test compounds exhibited moderate to significant antigrowth effect against the breast cancer (MCF-7) cell line and reduced cytotoxicity against the human embryonic kidney derived (Hek293-T) cell line compared to the anticancer drug, doxorubicin. The anti-oxidation potential of the test compounds was evaluated spectrophotometrically using the nitric oxide (NO) radical scavenging assay. A cell-based antioxidant activity assay involving lipopolysaccharide (LPS) induced reactive oxygen species production in the MCF-7 and Hek293-T cells revealed their potential to mitigate against oxidative stress. Molecular docking analysis revealed hydrogen bonding, hydrophobic and π-π stacking interactions to play a significant role in the binding affinity and interactions of the test compounds with amino acid residues in the active sites of the test enzymes.