ArticleDrug design, development and therapy2016
Flurbiprofen-antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling.
Article in Drug design, development and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 32 citations in OpenAlex.
- Coumarin-Based Prodrugs: Therapeutic Promise or Still Confined to Preclinical Exploration?Pharmaceutics · 2026Review
- Therapeutic Perspective of Prodrugs of Non-Steroidal Anti-Inflammatory Drugs and Antioxidants: An Approach to Reduce Toxicity and Enhance Efficacy.Current topics in medicinal chemistry · 2026Review
- Perioperative Flurbiprofen Axetil Administration and Acute Kidney Injury After Non-Cardiac Surgery: A Retrospective Cohort Study.Drug design, development and therapy · 2026Article
- Anti-Inflammatory Activity of Thymol and Thymol-Rich Essential Oils: Mechanisms, Applications, and Recent Findings.Molecules (Basel, Switzerland) · 2025Review
- Phytophenols as Promoieties for Prodrug Design.Current drug discovery technologies · 2025Review
- Fabrication, In Vitro and In Vivo Evaluation of Non-Ordered Mesoporous Silica-Based Ternary Solid Dispersions for Enhanced Solubility of Flurbiprofen.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Galactosylated Prodrugs: A Strategy to Improve the Profile of Nonsteroidal Anti-Inflammatory Drugs.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Fluconazole-COX Inhibitor Hybrids: A Dual-Acting Class of Antifungal Azoles.Journal of medicinal chemistry · 2022Article
- Flurbiprofen suppresses the inflammation, proliferation, invasion and migration of colorectal cancer cells via COX2.Oncology letters · 2020Article
- Dexibuprofen amide derivatives as potential anticancer agents: synthesis, in silico docking, bioevaluation, and molecular dynamic simulation.Drug design, development and therapy · 2019Article
- Antihyperlipidemic studies of newly synthesized phenolic derivatives: in silico and in vivo approaches.Drug design, development and therapy · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer's yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug.
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