Structure−Activity Relationships of Pentacyclic Triterpenoids as Inhibitors of Cyclooxygenase and Lipoxygenase Enzymes
Pentacyclic triterpenes may be active agentsand provide a rich natural resource of promising compoundsfor drug development. The inhibitory activities of 29 naturaloleanane and ursane pentacyclic triterpenes were evaluatedagainst four major enzymes involved in the inflammatoryprocess: 5-LOX, 15-LOX-2...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | Ecuador |
| Institución: | Universidad Regional Amazónica |
| Repositorio: | Repositorio Universidad Regional Amazónica |
| OAI Identifier: | oai:repositorio.ikiam.edu.ec:RD_IKIAM/328 |
| Acceso en línea: | http://repositorio.ikiam.edu.ec/jspui/handle/RD_IKIAM/328 https://doi.org/10.1021/acs.jnatprod.9b00538 |
| Access Level: | acceso abierto |
| Palabra clave: | Entacyclic Triterpenoids Inhibitors Enzymes Cyclooxygenase and Lipoxygenase |
| Sumario: | Pentacyclic triterpenes may be active agentsand provide a rich natural resource of promising compoundsfor drug development. The inhibitory activities of 29 naturaloleanane and ursane pentacyclic triterpenes were evaluatedagainst four major enzymes involved in the inflammatoryprocess: 5-LOX, 15-LOX-2, COX-1, and COX-2. It was foundthat 3-O-acetyl-β-boswellic acid potently inhibited human 15-LOX-2 (IC50= 12.2±0.47μM). Analysis of the structure−activity relationships revealed that the presence of a hydroxygroup at position 24 was beneficial in terms of both 5-LOXand COX-1 inhibition. Notably, the introduction of acarboxylic acid group at position 30 was important for dual5-LOX/COX inhibitory activity; furthermore, its combination with a carbonyl group at C-11 considerably increased 5-LOXinhibition. Also, the presence of anα-hydroxy group at C-2 or a carboxylic acid group at C-23 markedly suppressed the 5-LOXactivity. The presentfindings reveal that the types and configurations of polar moieties at positions C-2, -3, -11, -24, and -30 areimportant structural aspects of pentacyclic triterpenes for their potential as anti-inflammatory lead compounds. |
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