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-beta-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 beta-OH iso-seco-tanapartholide over the alpha:beta-OH diastereoisomeric mixture. The highest potency, however, was mainly the function of the enhanced lipophilicity of the molecule.