ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Study of antioxidant, antimicrobial, and α-glucosidase inhibitory activities of symmetrical N,N′-methylene bisamides and their catalyzed synthesis with humic acid

Karima Aoues, Hamzah Basil Mohammed, Samer Saleem Alshkarchy, Hamad AlMohamadi, Majid S. Jabir, Vinay Kumar Verma, Karthikeyan Jayabalan, Renu Sharma, Abhayveer Singh, and Monther Khadem

Laboratory of Food Science Technology and Sustainable Development, Faculty of Nature and Life Sciences, University of Blida, Blida, Algeria

E-mail: aoues_karima@univ-blida.dz

Received: 27 October 2025  Accepted: 9 May 2026

Abstract:

A diverse array of symmetrical N,N′-methylene bisamides (1a–21a) were successfully synthesized by reacting various aromatic/hetero-aromatic/aliphatic aldehydes with benzamide or acetamide in ethanol as a green solvent at 50 °C, utilizing humic acid (HA) as an available, non-toxic, and biodegradable organocatalyst. Key advantages of this green approach include excellent to good yields (84–98%), short reaction times (6–25 min), optimized synthesis and characterization of novel derivatives (18a–21a), low catalyst loading (20 mg), excellent functional group tolerance, and the reusability of HA for up to five runs, all without using toxic metal catalysts. The synthesized derivatives were then subjected to comprehensive biological validation covering antioxidant, antibacterial, and enzyme inhibitory activities. Regarding antioxidant potential, the DPPH scavenging assay demonstrated that derivative 20a was the most active (IC₅₀ ≈ 52.78 µg/mL). In antibacterial screening, performed by the broth microdilution method against common pathogens such as S. aureus and E. coli, the minimum inhibitory concentrations (MICs) for the most active analogues fell within the 25–100 µg/mL range. Most significantly, the biological validation for antidiabetic properties showed that all synthesized compounds were superior inhibitors of α-glucosidase compared to the reference drug acarbose (IC₅₀ = 447 µM). Specifically, compound 19a exhibited the strongest inhibitory effect, with an IC₅₀ value of 200 µM. These results validate the effectiveness of the green synthetic pathway in generating potent bioactive molecules suitable for potential therapeuti applications.

Graphical abstract

Keywords: Biodegradable organocatalyst; Symmetrical bisamides; Multicomponent reactions; Biological properties

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-05039-2

Chemical Papers 80 (9) 10717–10728 (2026)