Design and synthesis of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole: structural elucidation, DFT insights, and preliminary in silico biological evaluation
9 affiliations
- 1Laboratory of Molecular Chemistry, Materials, Catalysis and Environment, Faculty of Sciences and Technology, Sultan Moulay Slimane University
- 2Faculty of Science, Laboratory of Applied Chemistry and Environment (LCAE), University Mohammed Premier
- 3Bioorganique Chemistry Laboratory, Faculty of Science
- 4Department of Pesticide Chemistry and Technology, Faculty of Agriculture, Alexandria University
- 5Synthetic and Natural Products Drug Discovery Lab., Department of Chemistry, Government College Women University
- 6Applied Science Research Center, Applied Science Private University
- 7Department of Chemistry, Faculty of Science, Applied Science Private University
- 8X-Ray Diffraction Unit, RIAIDT, University of Santiago de Compostela, Campus VIDA
- 9Centro de Investigación de Procesos del Instituto Tecnológico Comfenalco (CIPTEC), Fundación Universitaria Tecnológico Comfenalco
Abstract
A multidisciplinary experimental and computational investigation of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole (compound 4) is reported. The compound was synthesized and characterized using FTIR, NMR, ESI–MS, and single-crystal X-ray diffraction, confirming its molecular structure and crystallographic features. To explore its possible pharmacological relevance, SwissTargetPrediction, molecular docking, molecular dynamics simulations, ADME/toxicity prediction, and DFT calculations were performed. SwissTargetPrediction suggested possible interactions with several protein classes, while molecular docking indicated favorable predicted binding poses of compound 4 within selected protein targets, particularly MurA and JAK2. Molecular dynamics simulations over 50 ns supported the preliminary stability of the corresponding protein–ligand complexes under the applied simulation conditions. ADME predictions suggested acceptable rule-based drug-likeness parameters, including predicted gastrointestinal absorption and blood–brain barrier permeability. However, in silico toxicity assessment also indicated potential safety alerts, including hepatotoxicity, neurotoxicity, and carcinogenicity risks, which require experimental verification. DFT calculations at the B3LYP/6-311G level, together with NBO, MEP, and Hirshfeld-related analyses, provided additional insight into the electronic distribution, charge-transfer behavior, and intermolecular interaction features of compound 4. Overall, the combined experimental and computational results identify compound 4 as a structurally confirmed oxadiazole scaffold with computationally suggested interactions toward selected biologically relevant targets. Nevertheless, its predicted biological properties should be considered preliminary and require further in vitro and in vivo validation.
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BibTeX
@article{hatim2026design,
title = {{Design and synthesis of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole: structural elucidation, DFT insights, and preliminary in silico biological evaluation}},
author = {Chaimaa Hatim and Abdessamad Benabbou and Said Jebbari and Mohamed R. Fouad and Rachid Touzani and Bushra Shakoor and Marwa Alaqarbeh and Hajiba Ouchetto and Mostafa Khouili and Zaragoza Verez Guillermo and Abdessamad Tounsi and Alejandro Morales-Bayuelo and Mohamed Anouar Harrad},
journal = {Scientific Reports},
year = {2026},
month = jun,
doi = {10.1038/s41598-026-59504-9},
url = {https://doi.org/10.1038/s41598-026-59504-9},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design and synthesis of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole: structural elucidation, DFT insights, and preliminary in silico biological evaluation
AU - Chaimaa Hatim
AU - Abdessamad Benabbou
AU - Said Jebbari
AU - Mohamed R. Fouad
AU - Rachid Touzani
AU - Bushra Shakoor
AU - Marwa Alaqarbeh
AU - Hajiba Ouchetto
AU - Mostafa Khouili
AU - Zaragoza Verez Guillermo
AU - Abdessamad Tounsi
AU - Alejandro Morales-Bayuelo
AU - Mohamed Anouar Harrad
PY - 2026
DA - 2026/06/01
JO - Scientific Reports
DO - 10.1038/s41598-026-59504-9
UR - https://doi.org/10.1038/s41598-026-59504-9
AB - A multidisciplinary experimental and computational investigation of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole (compound 4) is reported. The compound was synthesized and characterized using FTIR, NMR, ESI–MS, and single-crystal X-ray diffraction, confirming its molecular structure and crystallographic features. To explore its possible pharmacological relevance, SwissTargetPrediction, molecular docking, molecular dynamics simulations, ADME/toxicity prediction, and DFT calculations were performed. SwissTargetPrediction suggested possible interactions with several protein classes, while molecular docking indicated favorable predicted binding poses of compound 4 within selected protein targets, particularly MurA and JAK2. Molecular dynamics simulations over 50 ns supported the preliminary stability of the corresponding protein–ligand complexes under the applied simulation conditions. ADME predictions suggested acceptable rule-based drug-likeness parameters, including predicted gastrointestinal absorption and blood–brain barrier permeability. However, in silico toxicity assessment also indicated potential safety alerts, including hepatotoxicity, neurotoxicity, and carcinogenicity risks, which require experimental verification. DFT calculations at the B3LYP/6-311G level, together with NBO, MEP, and Hirshfeld-related analyses, provided additional insight into the electronic distribution, charge-transfer behavior, and intermolecular interaction features of compound 4. Overall, the combined experimental and computational results identify compound 4 as a structurally confirmed oxadiazole scaffold with computationally suggested interactions toward selected biologically relevant targets. Nevertheless, its predicted biological properties should be considered preliminary and require further in vitro and in vivo validation.
SN - 2045-2322
ER -