In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 57, No. 2 ( 2010-02-18), p. 219-225
Abstract:
The direct acylation of trimethoxyphenol (1) with substituted cinnamoyl chlorides followed by Fries rearrangement and cyclization afforded a practical route for the synthesis of novel baicalein derivatives 4 functionalized on the B-ring in good overall yields. In the methylthiazoletetrazolium bromide (MTT) assay, none of the synthetic polyhydroxyflavonoids were cytotoxic at concentrations up to 200 μm on lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages over 24 h, while in the same cells they significantly inhibited NO production. Among the derivatives, 4d (IC50 = 46.1 ± 0.3 μm) was found to exhibit the most potent activity compared with N-nitro-L-arginine methyl ester (L-NAME, IC50 & gt; 300 μm). Compounds 4b, 4e, 4f, 4h and 4i remarkably inhibited platelet aggregation induced by arachidonic acid and collagen in rabbit washed platelets compared with aspirin. Analysis of their structure-activity relationships indicated that, in the structural modification on the B-ring of baicalein (4a), introduction of appropriate electro-withdrawing substituents such as 2-CI (4b), 4-CI (4d), and 4-phenyl (4i) notably increased the potency on the inhibition of LPS-activated NO production and arachidonic acid- and collagen-induced aggregation. Baicalein itself was equally effective in the inhibition of LPS-activated NO production and collagen-induced aggregation but less active against arachidonic acid-induced aggregation. Our in-vitro results suggested that by appropriate structural modification of baicalein it may be possible to develop novel therapeutic agents against platelet-aggregation and inflammation.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/0022357055371
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
