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New Racemosol Derivatives as Potent Cyclooxygenase (COX) Inhibitors
Author(s) -
Songarsa Saiphon,
Rajviroongit Shuleewan,
SaeTang Darinee,
Hangbua Supa,
Kirtikara Kanyawim,
Kittakoop Prasat
Publication year - 2005
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200590133
Subject(s) - chemistry , stereochemistry , in vivo , cyclooxygenase , in vitro , structure–activity relationship , docking (animal) , active site , enzyme , molecule , pharmacology , biochemistry , organic chemistry , medicine , microbiology and biotechnology , nursing , biology
Racemosol ( 1 ) and 10‐ O ‐demethylracemosol ( 2 ), natural products from Bauhinia malabarica Roxb ., exhibit potent in vitro anti‐inflammatory activities against cyclooxygenase‐1 and ‐2 (COX‐1 and ‐2) enzymes. To investigate the structure–activity relationship (SAR) of these molecules, we prepared and fully characterized 17 derivatives by functionalizing one, two, or all three OH group(s) of 2 ( Scheme ). Both the size and polarity of the substituents as well as the substitution pattern in compounds 3a – q were found to be critical for anti‐inflammatory activity. The orientation of the drugs and their mode of binding were studied by molecular docking based on the known 3D structure of the complex between COX‐2 and the drug SC‐558. Whereas the monoacetoxy derivative 3h exhibited an equally potent inhibitory activity towards both COX‐1 and ‐2 ( Table 1 ), its diacetoxy congener 3i was slightly more selective toward COX‐2. In vivo anti‐inflammatory tests showed that 3i and 2 are slightly more active than the reference compound phenylbutazone ( Table 2 ).