INHIBITORY EFFECT OF DIARYLHEPTANOIDS ON NITRIC-OXIDE PRODUCTION IN ACTIVATED MURINE MACROPHAGES

Thirteen novel diarylheptanoids bearing a chalcone or a flavanone moie ty (1-13), a new curcumin derivative 1,2-dihydrobis(de-O-methyl)curcum in (14), and two known flavonoids (15 and 16) isolated from the seeds of Alpinia blepharocalyx K. Schum. were tested for their inhibitory ef fects on nitric oxide (NO) production in lipopolysaccaride (LPS)-activ ated murine macrophages J774.1 in vitro. All the tested compounds inhi bited NO production in a concentration-dependent manner (IC50=36-568 m u M). Among the compounds examined, blepharocalyxin B (13) was the mos t potent inhibitor of NO production (IC50=36 mu M). Analysis of the st ructure activity relationship among these novel diarylheptanoids led t o the conclusion that the position of attachment of a chalcone or a fl avanone to a diarylheptanoid does not affect their inhibitory potency although their presence in association causes a substantial enhancemen t of the inhibitory activity. Moreover, a conjugated double bond in a chalcone moiety potentiated the inhibitory activity. On the other hand , hexamethoxydeoxycalyxin A (17) and pentamethoxycalyxin B (18), a met hylated product of calyxin A (1) and an epimeric mixture of calyxin B, showed greatly reduced activity suggesting that phenolic hydroxyl gro ups are involved in the inhibitory activity.