New benzothiophene derivatives as dual COX-1/2 and 5-LOX inhibitors: synthesis, biological evaluation and docking study
| Autor: | Soad A.M. El-Hawash, Rasha A. Nassra, Mostafa M.M. El-Miligy, Hanan El-Messmary, Aly A. Hazzaa |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Thiophenes Pharmacology 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship In vivo Formaldehyde Drug Discovery medicine Animals Edema Humans Cyclooxygenase Inhibitors Lipoxygenase Inhibitors Stomach Ulcer Benzofuran Arachidonate 5-Lipoxygenase Chemistry Anti-Inflammatory Agents Non-Steroidal Benzothiophene Rats Molecular Docking Simulation 030104 developmental biology Docking (molecular) Cyclooxygenase 2 Celecoxib Meclofenamate Sodium Cyclooxygenase 1 Molecular Medicine Bioisostere Pharmacophore medicine.drug |
| Zdroj: | Future medicinal chemistry. 9(5) |
| ISSN: | 1756-8927 |
| Popis: | Aim: Simultaneous inhibition of 5-LOX/COX may enhance anti-inflammatory effects and reduce side effects. Hence, synthesis of novel dual inhibitors of 5-LOX/COX is an important strategy for treatment of inflammation. Results/methodology: The target compounds were designed to hybridize benzothiophene scaffold or its bioisostere benzofuran with various anti-inflammatory pharmacophore hetercycles through different atoms spacers. Compounds 4a, 4c, 4d, 5b, 7a, showed significant in vitro LOX inhibitory activity higher than that of meclofenamate sodium. Compounds 4b, 4e, 4f, 5a exhibited significant in vitro COX-2 inhibition higher than celecoxib and in vitro LOX inhibitory activity twice that of reference. These compounds elicited significant in vivo anti-inflammatory activities higher than celecoxib in formalin-induced paw edema test. Compound 4e exhibited gastrointestinal safety profile as celecoxib. The results were also consistent with the docking studies. Conclusion: Compound 4e could be considered as structural lead for the development of a new class of anti-inflammatory agents with better safety profile. |
| Databáze: | OpenAIRE |
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