Design and Synthesis of Triazole-Phthalimide Hybrids with Anti-inflammatory Activity
| Autor: | Moara Targino da Silva, Shalom Pôrto de Oliveira Assis, Caíque Silveira Martins da Fonseca, Carolina M B de Albuquerque Tenório, Gustavo M. Seabra, Ronaldo N. de Oliveira, Mirella P Sant'Anna, Vera Lúcia de Menezes Lima, Caroline F Brito Dos Santos, Filipe Torres da Silva |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
010405 organic chemistry
Chemistry Stereochemistry Anti-Inflammatory Agents Non-Steroidal Triazole Phthalimides General Chemistry General Medicine Triazoles 010402 general chemistry 01 natural sciences Acute toxicity 0104 chemical sciences Phthalimide chemistry.chemical_compound Structure-Activity Relationship Benzothiazole Docking (molecular) Amide Drug Design Drug Discovery Toxicity Moiety Animals Edema |
| Zdroj: | Chemicalpharmaceutical bulletin. 67(2) |
| ISSN: | 1347-5223 |
| Popis: | Phthalimido-alkyl-1H-1,2,3-triazole derivatives 3a-d and 4a-d were efficiently synthesized using 1,3-dipolar cycloaddition reaction. Anti-inflammatory activity and toxicity studies were performed. The results demonstrated that all the tested compounds reduced carrageenan-induced paw edema and indicated no lethality for toxicity against Artemia salina and acute toxicity in vivo (LD50 up to 1 g kg -1). Furthermore, the structure of phthalimide linked to phenyl group proved to be more active than the compounds containing benzothiazole moiety. Structural modifications such as removal of the phthalimide group and subsequent acetylation, to exemplify a non-cyclic amide, demonstrate that the phthalimide and triazole moieties are important for design of potent candidates with anti-inflammatory drug proprieties. Docking into the cyclooxygenase-2 (COX-2) confirms the importance of the phthalimide and triazole groups in the anti-inflammatory activity. The histopathological studies showed that the compounds 3a-d and 4a-d did not cause serious pathological lesions liver or kidneys. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|