Design, synthesis, antioxidant and antimicrobial activities of novel fluorinated azabicyclo–benzohydrazone hybrids supported by DFT, molecular docking, ADME, and PETRA-Osiris analyses
9 affiliations
- 1Department of Chemistry, Audisankara (Deemed to be University), Gudur, Andhra Pradesh, 524101, India; Corresponding authors.
- 2Chemistry Section, FEAT-Annamalai University, Annamalainagar, Tamil Nadu, 608002, India
- 3Department of Pharmaceutical Science, College of Pharmacy, Al Ain University, Al Ain, United Arab Emirates
- 4Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, 603103, India
- 5Department of Chemistry, Audisankara (Deemed to be University), Gudur, Andhra Pradesh, 524101, India
- 6Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu & Kashmir, 180001, India
- 7Department of Chemistry, RTM Nagpur University, Nagpur, 440 033, India; Corresponding authors.
- 8College of Natural and Computational Sciences, Chemistry Department, University of Gondar, P.O. Box, 196; Corresponding authors.
- 9Grigore T. Popa University of Medicine and Pharmacy Iasi, Iasi, Romania
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.
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BibTeX
@article{dar2026design,
title = {{Design, synthesis, antioxidant and antimicrobial activities of novel fluorinated azabicyclo–benzohydrazone hybrids supported by DFT, molecular docking, ADME, and PETRA-Osiris analyses}},
author = {Tanzeer Ahmad Dar and Thirunavukkarasu Balasankar and Khairi M. Fahelelbom and Mohd Arif Dar and Sujaha Gundeboiyna and Sumeer Ahmed and Ajmal R. Bhat and Birhanu Ayalew Tebeje and Gabriela Tataringa},
journal = {Results in Chemistry},
year = {2026},
month = oct,
doi = {10.1016/j.rechem.2026.103964},
url = {https://doi.org/10.1016/j.rechem.2026.103964},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design, synthesis, antioxidant and antimicrobial activities of novel fluorinated azabicyclo–benzohydrazone hybrids supported by DFT, molecular docking, ADME, and PETRA-Osiris analyses
AU - Tanzeer Ahmad Dar
AU - Thirunavukkarasu Balasankar
AU - Khairi M. Fahelelbom
AU - Mohd Arif Dar
AU - Sujaha Gundeboiyna
AU - Sumeer Ahmed
AU - Ajmal R. Bhat
AU - Birhanu Ayalew Tebeje
AU - Gabriela Tataringa
PY - 2026
DA - 2026/10/30
JO - Results in Chemistry
DO - 10.1016/j.rechem.2026.103964
UR - https://doi.org/10.1016/j.rechem.2026.103964
AB - 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.
SN - 2211-7156
ER -