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Design, synthesis, antioxidant and antimicrobial activities of novel fluorinated azabicyclo–benzohydrazone hybrids supported by DFT, molecular docking, ADME, and PETRA-Osiris analyses

Year: 2026

Type: article

Abstract: A novel series of fluorine-substituted azabicyclo–benzohydrazone hybrids (4F-ABN-Hyd, 6a–6e ) was designed and synthesized through the condensation of 4-fluorobenzohydrazide with structurally diverse azabicyclo[3.3.1]nonan-9-one derivatives. The synthesized compounds were structurally characterized by FT-IR, 1 H NMR, and 13 C NMR spectroscopy, confirming the formation of the targeted hydrazone framework. Antibacterial activity was evaluated against five bacterial strains, including two Gram-positive bacteria, Bacillus subtilis (ATCC 25922) and Staphylococcus aureus (ATCC 25923), and three Gram-negative bacteria, Klebsiella pneumoniae (ATCC 25955), Escherichia coli (ATCC 25922), and Pseudomonas aeruginosa (ATCC 27853). Antifungal activity was assessed against four fungal isolates, namely Aspergillus flavus (AF-CI-05), Aspergillus niger (AN-CI-04), Candida albicans (CA/OL/01–15), and Candida sp. (CK-CI-02). Among the synthesized derivatives, 6b and 6c exhibited the strongest antioxidant activity, whereas 6d and 6e demonstrated superior antibacterial and antifungal effects. Density functional theory (DFT) calculations were performed at the B3LYP/6-311G(d,p) level, providing insights into the molecular electronic structure and chemical reactivity of the compounds. In silico ADME and drug-likeness assessments indicated that 6a–6c possessed particularly favorable pharmacokinetic characteristics. Molecular docking studies further supported the biological findings, with the synthesized compounds exhibiting favorable binding affinities, reflected by Glide scores ranging from −6.38 to −6.51 kcal/mol , and forming stabilizing hydrogen-bonding and hydrophobic interactions within the target binding site. Additional evaluation using PETRA and Osiris revealed favorable drug-likeness, and low predicted toxicity for the majority of the derivatives, with 6a, 6b, and 6e emerging as particularly promising candidates. The combined experimental and computational findings demonstrate that the 4F-ABN-Hyd scaffold represents a promising and versatile molecular framework for the development of antioxidant and antimicrobial agents.

Source: Results in Chemistry

DOI: 10.1016/j.rechem.2026.103964