A New Nonpeptide Tachykinin NK1 Receptor Antagonist Isolated from the Plants of Compositae
| Autor: | Kazuhito Furukawa, Yukari Konishi, Ko Nakamura, Masanori Otsuka, Hisashi Yago, Takashi Ogino, Kunihiko Higashiura, Kaoru Okamoto, Atsushi Yamamoto |
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| Rok vydání: | 2002 |
| Předmět: |
Guinea Pigs
Spermine Substance P CHO Cells Alkenes Asteraceae Pharmacology Binding Competitive Guinea pig Structure-Activity Relationship chemistry.chemical_compound Neurokinin-1 Receptor Antagonists Ileum Cricetinae Tachykinins Drug Discovery Animals Humans Receptor Aza Compounds biology Plant Extracts Chemistry Antagonist Chamomile Biological activity General Chemistry General Medicine Receptors Neurokinin-1 biology.organism_classification Matricaria chamomilla Biochemistry NK1 receptor antagonist Muscle Contraction |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 50:47-52 |
| ISSN: | 1347-5223 0009-2363 |
| Popis: | To find new tachykinin NK1 receptor antagonists from natural sources, we examined the tachykinin antagonist activity in the extracts of approximately 200 species of plants by the use of isolated guinea pig ileum. As a result, we discovered a novel and potent NK1 receptor antagonist in the extract of dried flowers of Matricaria chamomilla L. (chamomile). The structure of the antagonist was established as N1,N5,N10,N14-tetrakis[3-(4-hydroxyphenyl)-2-propenoyl]-1,5,10,14-tetraazatetradecane (tetracoumaroyl spermine, 1a). The Ki values of 1a, estimated from the inhibitory action on the substance P (SP)-induced contraction of the guinea pig ileum and the inhibition of the binding of [3H][Sar9, Met(O2)11]SP to human NK1 receptors, were 21.9 nM and 3.3 nM, respectively. 1a is the first potent NK1 receptor antagonist from natural sources and it has a unique structure of a polyacylated spermine. 1a was concentrated in pollen of Matricaria chamomilla L. and was also found in the extracts of flowers of other four species of Compositae. In addition, we found N1,N5,N10-tris[3-(4-hydroxyphenyl)-2-propenoyl]-1,5,10,14-tetraazatetradecane (2) as a new compound in the extract of flowers of Matricaria chamomilla L., which did not exhibit any tachykinin antagonist activity. A number of related compounds were synthesized, and the structure-activity relationship was studied. |
| Databáze: | OpenAIRE |
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