Ganoderma cochlear Metabolites as Probes to Identify a COX-2 Active Site and as in Vitro and in Vivo Anti-Inflammatory Agents

(±)-Dispirocochlearoids A–C (1–3), meroterpenoids with a 6/6/5/6/6/6 ring system, were isolated from Ganoderma cochlear. 1–3 are selective COX-2 inhibitors with an IC50 value of (−)-2 at 386 nM. Site-directed mutagenesis identified His351 as a COX-2 active site. In vivo anti-inflammatory activities of (−)-2 were performed against acute lung injury in mice.