New enaminone derivatives of 6-hydroxy-4,7-dimethoxy-benzofuran-5-yl scaffold: Synthesis, antimicrobial and antioxidant activities, and molecular docking studies as potential DNA gyrase B and DHFR inhibitors

Sediek, Ashraf A; El-Mowafi, Shaima A.; Younis, Ahmed; Abdelaziz, Mohamed S.; Sabry, Eman

doi:10.21608/ejchem.2024.324405.10532

New enaminone derivatives of 6-hydroxy-4,7-dimethoxy-benzofuran-5-yl scaffold: Synthesis, antimicrobial and antioxidant activities, and molecular docking studies as potential DNA gyrase B and DHFR inhibitors

Document Type : Original Article

Authors

¹ National Research Centre – Industrial Research Institute – Pesticide Chemistry Department.

² Peptide Chemistry Department, National Research Centre, 12622 Dokki, Giza,

³ National Research Centre

⁴ Microbial Chemistry Department, Biotechnology Research Institute, National Research Centre, 12622 Dokki, Giza, Egypt

⁵ Chemical Industries Institute, National Research Centre, 12622 Dokki, Giza, Egypt;

10.21608/ejchem.2024.324405.10532

Abstract

A new series of enaminone derivatives of 6-hydroxy-4,7-dimethoxy-benzofuran scaffold have been synthesized using a simple and practical coupling reaction of enaminone 2 with different primary amines to give benzofuran derivatives 3a-j. The same enaminone was allowed to interact with different hydrazonyl halide derivatives 4a-d to yield the corresponding pyrazole derivatives 5a-d. All derivatives were characterized with IR, 1H NMR and 13C NMR techniques. The antimicrobial activity of the new compounds was determined for Gram-positive and Gram-negative bacterial strains using agar well diffusion method. The MIC assay was then assessed. Further in vitro assays showed that 3g moderately inhibited DNA gyrase, while 5b weakly inhibited DNA gyrase. Additionally, both compounds 3g and 5b moderately inhibited DHFR in vitro. Compound 3g was shown to be able to form stable complexes with both DNA gyrase and DHFR, as demonstrated by the docking studies. All compounds except 3e presented a prominent total antioxidant activity

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