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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

Year: 2025

Type: article

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. • Series of 6-methoxy/hydroxy substituted 7-acetyl-2-aryl-5-bromobenzofurans were synthesized. • Characterization of both series was done by spectroscopy (NMR & IR) and X-ray diffraction. • In vitro anti-enzymatic (α-glucosidase, α-amylase & protein tyrosine phosphatase 1 beta) activity. • In vitro cytotoxicity and nitric oxide radical scavenging assays. • Molecular docking confirmed the binding interactions within the active sites of the test enzymes.

Source: Bioorganic Chemistry

DOI: 10.1016/j.bioorg.2025.108465

Authors: Abdufatai T. Ajiboye, Jackson K. Nkoana, Garland K. More, Ahmed A. Elhenawy, Malose J. Mphahlele

Institutions: University of South Africa, Al-Azhar University

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,240