Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies
Cell function depends on redox homeostasis, and several diseases are linked to its disruption. The relative amounts of reduced and oxidised glutathione play a major role in controlling redox balance. Redox equilibrium is essential for a number of physiological functions, including protein folding an...
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Elsevier
2025-07-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625004916 |
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| author | Mohammed Salah Ayoup Islam Shawki Hamida Abdel-Hamid Doaa A. Ghareeb Samah Ashraf Mohamed El-Atawy Nuha S. Alharbi Jawaher Y. Al Nawah Magda M.F. Ismail |
| author_facet | Mohammed Salah Ayoup Islam Shawki Hamida Abdel-Hamid Doaa A. Ghareeb Samah Ashraf Mohamed El-Atawy Nuha S. Alharbi Jawaher Y. Al Nawah Magda M.F. Ismail |
| author_sort | Mohammed Salah Ayoup |
| collection | DOAJ |
| description | Cell function depends on redox homeostasis, and several diseases are linked to its disruption. The relative amounts of reduced and oxidised glutathione play a major role in controlling redox balance. Redox equilibrium is essential for a number of physiological functions, including protein folding and cell signalling. Thus, redox imbalance has been linked to a number of clinical illnesses, including diabetes, cancer, and neurodegenerative diseases. Here, we designed and synthesized a new library of 3, 5-diaryl-1,2,4-oxadiazole derivatives, evaluated by scavenging the dangerous free radicals. The produced oxadiazoles are all examined by spectroscopic and micro-analytical techniques. Three assays were used to assess the antioxidant properties: total antioxidant (FRAP), DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals, and nitric oxide. When nitric oxide, DPPH, and FRAP were combined, the results were nearly same. Key findings revealed that compounds 12, 10, and 13 exhibited superior NO scavenging activity with IC50 values of 35.59 ± 1.3, 37.41 ± 1.1, and 40.54 ± 1.3 μM, respectively. DPPH assay results indicated potent radical scavenging activity, with IC50 values of 67.08 ± 1.1 to 99.94 ± 1.1 μM. In the FRAP assay, compounds 15, 18, 11, 10, and 12 demonstrated the highest antioxidant activities, which were consistent with the results of the other assays. Computational predictions of the physicochemical attributes, pharmacokinetic profiles, and drug-likeness data of all the synthesized compounds indicated that our hits may be introduced as drug-like candidates because they showed appropriate criteria in medicinal chemistry and drug-likeness values which hopefully can alleviate poor biopharmaceutical properties of many antioxidants. |
| format | Article |
| id | doaj-art-320e300888824375a0ceb4b08df7a6ea |
| institution | DOAJ |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-320e300888824375a0ceb4b08df7a6ea2025-08-20T03:02:26ZengElsevierResults in Chemistry2211-71562025-07-011610250810.1016/j.rechem.2025.102508Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studiesMohammed Salah Ayoup0Islam Shawki1Hamida Abdel-Hamid2Doaa A. Ghareeb3Samah Ashraf4Mohamed El-Atawy5Nuha S. Alharbi6Jawaher Y. Al Nawah7Magda M.F. Ismail8Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt; Corresponding author at: Department of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, EgyptDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria, EgyptBio-screening and preclinical trial lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt; Center of Excellence for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industry Development Center, City of Scientific Research & Technological Applications (SRTA-city), New Borg El Arab, Alexandria, Egypt; Research Projects unit, Pharos University in Alexandria; Canal El Mahmoudia Street, Beside Green Plaza Complex, 21648, Alexandria, EgyptBio-screening and preclinical trial lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, EgyptDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt; Chemistry Department, College of Science at Yanbu, Taibah University, Yanbu 46423, Saudi Arabia; Corresponding author at: Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.Department of Chemistry, College of Science, Taibah University, Madinah, Saudi ArabiaDepartment of Chemistry, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, EgyptCell function depends on redox homeostasis, and several diseases are linked to its disruption. The relative amounts of reduced and oxidised glutathione play a major role in controlling redox balance. Redox equilibrium is essential for a number of physiological functions, including protein folding and cell signalling. Thus, redox imbalance has been linked to a number of clinical illnesses, including diabetes, cancer, and neurodegenerative diseases. Here, we designed and synthesized a new library of 3, 5-diaryl-1,2,4-oxadiazole derivatives, evaluated by scavenging the dangerous free radicals. The produced oxadiazoles are all examined by spectroscopic and micro-analytical techniques. Three assays were used to assess the antioxidant properties: total antioxidant (FRAP), DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals, and nitric oxide. When nitric oxide, DPPH, and FRAP were combined, the results were nearly same. Key findings revealed that compounds 12, 10, and 13 exhibited superior NO scavenging activity with IC50 values of 35.59 ± 1.3, 37.41 ± 1.1, and 40.54 ± 1.3 μM, respectively. DPPH assay results indicated potent radical scavenging activity, with IC50 values of 67.08 ± 1.1 to 99.94 ± 1.1 μM. In the FRAP assay, compounds 15, 18, 11, 10, and 12 demonstrated the highest antioxidant activities, which were consistent with the results of the other assays. Computational predictions of the physicochemical attributes, pharmacokinetic profiles, and drug-likeness data of all the synthesized compounds indicated that our hits may be introduced as drug-like candidates because they showed appropriate criteria in medicinal chemistry and drug-likeness values which hopefully can alleviate poor biopharmaceutical properties of many antioxidants.http://www.sciencedirect.com/science/article/pii/S2211715625004916DesignSynthesis1,2,4-OxadiazoleAntioxidantIn silico |
| spellingShingle | Mohammed Salah Ayoup Islam Shawki Hamida Abdel-Hamid Doaa A. Ghareeb Samah Ashraf Mohamed El-Atawy Nuha S. Alharbi Jawaher Y. Al Nawah Magda M.F. Ismail Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies Results in Chemistry Design Synthesis 1,2,4-Oxadiazole Antioxidant In silico |
| title | Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies |
| title_full | Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies |
| title_fullStr | Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies |
| title_full_unstemmed | Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies |
| title_short | Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies |
| title_sort | antioxidant evaluation of novel 3 aryl 5 phenyloxy 1 2 4 oxadiazoles as radical scavengers synthesis characterization and adme studies |
| topic | Design Synthesis 1,2,4-Oxadiazole Antioxidant In silico |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625004916 |
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