Bis-chalcone analogues as potent NO production inhibitors and as cytotoxic agents.

Chalcones have a distinctive 1,3-diarylpropenone skeleton and exert numerous biological effects. Using a one-step Claisen-Schmidt condensation, we synthesized eleven bis-chalcones (3-13) and three acetyl chalcones (14-16) from substituted aldehydes and diacetylresorcinol. The compounds were tested for in vitro cytotoxic activity against four human cancer cell lines (A549, DU145, KB, and KB-VIN) and inhibition of NO production in lipopolysaccharide (LPS)-activated microglial cells. Among them, four compounds (3, 5, 6, and 13) showed significant cytotoxic activity with EC(50) values ranging from 1.57 to 5.14 µM, and seven compounds (3, 5-8, 10, and 13) displayed potent anti-inflammatory activity by inhibiting NO production with IC(50) values ranging from 0.95 to 8.65 µM. A mechanism of action study of active compounds 6 and 7 discovered that these compounds down-regulated iNOS expression by inhibiting p65 NF-κB activation/nuclear translocation due to prevention of IκBα degradation. Structure-activity relationship (SAR) findings are also discussed.

Structure-activity relationships of chalcone analogs as potential inhibitors of ADP- and collagen-induced platelet aggregation.

In an effort to develop potent antiplatelet agents, 12 O-prenylated (2-13) and 10 O-allylated (14-23) chalcones were synthesized and screened for in vitro inhibitory effects on aggregation of washed rabbit platelets induced by ADP (20 µM) and collagen (10 µg/mL). In addition, the platelet aggregation activity of previously synthesized Mannich bases of heterocyclic chalcones (MBHC) (24-62) was evaluated. The preliminary structure-activity relationships suggested that the antiplatelet activity was governed to a great extent by the presence of a pyridyl ring-B and a hydroxy group at position C-3' in ring-A of the MBHC templates.

Cytochrome P3A4 inhibitors and other constituents of Fibraurea tinctoria.

Four new furanoditerpenoids, fibrauretin A ( 1), fibrauretinoside A ( 2), epi-fibrauretinoside A ( 3), and epi-12-palmatoside G ( 4), and a new ecdysteroid glucoside, fibraurecdyside A ( 5), together with seven known compounds including two furanoditerpenoids ( 6 and 7), an ecdysteroid ( 8), and four quaternary protoberberine alkaloids ( 9- 12) were isolated from the stems of Fibraurea tinctoria. The structures of 1- 5 were established on the basis of spectroscopic evidence. Among these compounds, palmatine ( 9) and jatrorrhizine ( 10) showed inhibitory effects against cytochrome P450 3A4 (CYP3A4) with IC 50 values of 0.9 and 2.1 microM, respectively.