OBJECTIVES: Quillaic acid is the major aglycone of the widely studied saponins of the Chilean indigenous tree Quillaja saponaria Mol. The industrial availability of quillaja saponins and the extensive functionalization of this triterpenoid provide unique opportunities for structural modification and pose a challenge from the standpoint of selectivity in regard to one or the other secondary alcohol group, the aldehyde, and the carboxylic acid functions. The anti-inflammatory activity of this sapogenin has not been studied previously and it has never been used to obtain potential anti-inflammatory derivatives. METHODS: A series of quillaic acid derivatives were prepared and subjected to topical assays for the inhibition of inflammation induced by arachidonic acid or phorbol ester. KEY FINDINGS: Quillaic acid exhibited strong topical anti-inflammatory activity in both models. Most of its derivatives were less potent, but the hydrazone 8 showed similar potency to quillaic acid in the TPA assay. CONCLUSIONS: The structural modifications performed and the biological results suggest that the aldehyde and carboxyl groups are relevant to the anti-inflammatory activity in these models.
OBJECTIVES:Quillaic acid is the major aglycone of the widely studied saponins of the Chilean indigenous tree Quillaja saponaria Mol. The industrial availability of quillajasaponins and the extensive functionalization of this triterpenoid provide unique opportunities for structural modification and pose a challenge from the standpoint of selectivity in regard to one or the other secondary alcohol group, the aldehyde, and the carboxylic acid functions. The anti-inflammatory activity of this sapogenin has not been studied previously and it has never been used to obtain potential anti-inflammatory derivatives. METHODS: A series of quillaic acid derivatives were prepared and subjected to topical assays for the inhibition of inflammation induced by arachidonic acid or phorbol ester. KEY FINDINGS:Quillaic acid exhibited strong topical anti-inflammatory activity in both models. Most of its derivatives were less potent, but the hydrazone 8 showed similar potency to quillaic acid in the TPA assay. CONCLUSIONS: The structural modifications performed and the biological results suggest that the aldehyde and carboxyl groups are relevant to the anti-inflammatory activity in these models.
Authors: Nilufar Z Mamadalieva; Fadia S Youssef; Hidayat Hussain; Gokhan Zengin; Adriano Mollica; Nawal M Al Musayeib; Mohamed L Ashour; Bernhard Westermann; Ludger A Wessjohann Journal: Molecules Date: 2021-10-20 Impact factor: 4.411