Development of benzofuran-based 1,3,4-oxadiazole hybrids as potential BRD4 inhibitors and antidiabetic activities

Date

2026-10-15

Author

UZUNER, UĞUR
İzgi, Samet
Celik-Uzuner, Selcen
Sengul, Ibrahim F.
AYAZOĞLU DEMİR, ELİF
Bingul, Murat
Sahin, Hasan
Son, Çağdaş Devrim
Uslu Uçar, Tugçe Nur
Kandemir, Hakan

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This study aimed to design and synthesize novel benzofuran-based 1,3,4-oxadiazole hybrids and evaluate their potential as bromodomain-containing protein 4 (BRD4) inhibitors with antidiabetic activities. For this purpose, 4,6-dimethoxy-2-phenylbenzofuran-7-yl-1,3,4-oxadiazoles were successfully synthesized through the reaction of 4,6-dimethoxy-2-phenylbenzofuran-7-carbaldehydes with benzohydrazide and 4-methylbenzohydrazide, leading to the corresponding benzofuran-7-carbohydrazides. These intermediates were then subjected to an iodine-mediated synthetic route, which resulted in the formation of the targeted benzofuran-based 1,3,4-oxadiazoles. The compounds 6a and 6d were cytotoxic for both cancerous (breast and lung) cells and their normal counterpart cell groups; however, compounds 7a-d did not induce significant cytotoxicity in any of the tested cell lines. Molecular docking predictions, supported by time-resolved fluorescence energy transfer TR-FRET assays, revealed that the compounds 7d and 6d are promising candidates for inhibiting the activity of BRD4 BD1. In addition, the synthesized compounds were evaluated for their antidiabetic potential through α-glucosidase and α-amylase inhibition assays. The carbohydrazide intermediates demonstrated superior enzyme inhibitory activity compared to the corresponding oxadiazole derivatives, with compound 6a emerging as the most potent dual inhibitor, showing stronger α-glucosidase inhibition than Acarbose. Overall, these findings suggest that benzofuran-based hybrids represent promising scaffolds for the development of dual-acting as BRD4 inhibitors and compounds exhibiting antidiabetic activity.

Subject Keywords

1,3,4-oxadiazoles, Anti-diabetic, Benzofuran, BRD4 inhibitors, Docking study

URI

https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105039703002&origin=inward
https://hdl.handle.net/11511/119543

Collections

Department of Biology, Article