Cytotoxic and Anti‐Inflammatory Activity of 3,19‐Isopropylidene‐/Arylidene‐Andrographolide Analogs

Abstract

AbstractA series of 3,19‐isopropylidene‐/or arylidene‐andrographolide analogs were synthesized and their structures were confirmed by NMR spectroscopic methodology. Twenty‐five analogs were evaluated for their in vitro cytotoxic activity against HT‐29, HepG2 and LNCaP cancer cell lines based on the sulforhodamine B (SRB) assay. Analog 2 f exhibited the most potent cytotoxic activity, with IC50 values of 11.14 and 9.25 μM on HepG2 and LNCaP cancer cell lines, respectively. Esterification of hydroxy functional group at position C‐14 in andrographolide analogs, 2 a and 2 b, showed somewhat higher cytotoxicity than the precursor. In addition, andrographolide analogs (2 a–2 d, 2 f, 3 a, 4 a and 4 h) were evaluated for the NO inhibitory activity in the LPS stimulated RAW264.7 macrophages. The most active analog 2 a significantly reduced nitric oxide (NO) production from LPS stimulated RAW264.7 cells, with IC50 values of 0.34±0.02 μM providing encouraging results for anti‐inflammatory compound development.