Excavation of lead compounds that inhibit mast cell degranulation by combinatorial chemistry and activity-guided.
An allergic reaction ensues after antigen binds to mast cell or basophil high affinity IgE receptor, Fc epsilonRI, resulting in degranulation of various inflammatory mediators that produce various allergic symptoms. In this study, i) we isolated the active component for the inhibition of mast cell degranulation from the extract of leaves of Castanea crenata and identified it as quercetin; ii) we established the total synthesis procedure of quercetin; iii) using quercetin as positive control, we excavated some lead compounds that possess inhibitory activities for mast cell degranulation by screening the chemical libraries of 1,3-oxazolidine derivatives prepared by solid phase combinatorial chemistry. Some of 1,3-oxazolidine compounds possessing acetyl and 3',4'-dichlorophenyl group displayed strong inhibitory activities on Fc epsilonRI-mediated mast cell degranulation, suggesting that they can be used as lead compounds for the development of anti-allergic agents.
Hahn
Hoh-Gyu
HG
College of Pharmacy, Drug Development Research Institute, Chonnam National University, Kwang-Ju, 500-757, Korea.
Oh
Heong Sub
HS
Cheon
Seung Hoon
SH
Oak
Min Ho
MH
Kim
Young-Ran
YR
Kim
Kyeong-Man
KM
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D029962:Fagaceae; D007854:Lead / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves; D051381:Rats
D010936:Plant Extracts; D007854:Lead