Structure–activity relationship of seco-tanapartholides isolated from Achillea falcata for inhibition of HaCaT cell growth

Four sesquiterpene lactones were isolated from Achillea falcata, through bioassay-guided fractionation, based on their differential ability to affect HaCaT cell growth. Identified seco-tanapartholides: 3-β-methoxy-iso-seco-tanapartholide (1), tanaphillin (2), iso-seco-tanapartholide (3), and 8-hydroxy-3-methoxy-iso-seco-tanaparatholide (4) were found to differentially decrease keratinocyte cell viability. In addition, the stereoselectivity, lipophilicity, and number and position of hydroxyl groups present in these compounds were correlated with their biological activities for HaCaT cell growth inhibition. Statistical analyses confirmed an enhanced potency of the β-OH iso-seco-tanapartholide over the α:β-OH diastereoisomeric mixture. The highest potency, however, was mainly the function of the enhanced lipophilicity of the molecule.

Graphical abstractIC50 values of four seco-tanapartholides differing in chemical properties and number and position of substituents showed that 3-β-methoxy-iso-seco-tanapartholide most potently inhibits keratinocyte cell proliferation due to its enhanced lipophilicity.Figure optionsDownload full-size imageDownload as PowerPoint slide