Abstract
Thirty-two compounds were isolated from the dichloromethane, ethyl acetate and methanol extracts of Ledebouria socialis and Ledebouria ovatifolia. Of these nine were novel and are depicted in Fig. 1. Concurrently the synthesis of the biologically active (E)-hinokiresinol (Compound T) was performed using MOM-protection. The synthetic scheme was completed in overall yields of 20% (Fig. 2). During an acid elimination an unexpected rearrangement occurred to form a 3-vinyl-phenylindane. After an investigation into the mechanism using different substituents on the first ring, the mechanism was found to be an electrophilic substitution (Fig. 3). Both the isolated and synthesised derivatives were tested for anti-inflammatory activity using a fluorescence based assay and the cyclooxygenase enzymes (COX-1 and COX-2) (Fig. 4). Compounds were tested for both their inhibitory concentration (IC50) against COX-2 and their selectivity against COX-1. Compound T was found to have at least twenty times selectivity for COX-2 and an IC50 of 1 μM. Compound 23 was found to have a larger inhibitory concentration, 3 μM, but was completely selective for COX-2 at 20 μM. Compound 25 was not selective and had an IC50 of 1μM for COX-2 and 3μM for COX-1. The percentage activity of the non-selective compounds was also calculated.