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ID: ALA4414666

Journal: J Nat Prod

Title: Structure-Activity Relationships of Pentacyclic Triterpenoids as Inhibitors of Cyclooxygenase and Lipoxygenase Enzymes.

Authors: Vo NNQ, Nomura Y, Muranaka T, Fukushima EO.

Abstract: Pentacyclic triterpenes may be active agents and provide a rich natural resource of promising compounds for drug development. The inhibitory activities of 29 natural oleanane and ursane pentacyclic triterpenes were evaluated against four major enzymes involved in the inflammatory process: 5-LOX, 15-LOX-2, COX-1, and COX-2. It was found that 3-O-acetyl-β-boswellic acid potently inhibited human 15-LOX-2 (IC50 = 12.2 ± 0.47 μM). Analysis of the structure-activity relationships revealed that the presence of a hydroxy group at position 24 was beneficial in terms of both 5-LOX and COX-1 inhibition. Notably, the introduction of a carboxylic acid group at position 30 was important for dual 5-LOX/COX inhibitory activity; furthermore, its combination with a carbonyl group at C-11 considerably increased 5-LOX inhibition. Also, the presence of an α-hydroxy group at C-2 or a carboxylic acid group at C-23 markedly suppressed the 5-LOX activity. The present findings reveal that the types and configurations of polar moieties at positions C-2, -3, -11, -24, and -30 are important structural aspects of pentacyclic triterpenes for their potential as anti-inflammatory lead compounds.

CiteXplore: 31774676

DOI: 10.1021/acs.jnatprod.9b00538