CC BY-NC-ND 4.0 · PMIO 2017; 4(02): e43-e51
DOI: 10.1055/s-0043-106742
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Tetra-cis/trans-Coumaroyl Polyamines as NK1 Receptor Antagonists from Matricaria chamomilla

Sait Byul Park1, Kwangho Song1, Yeong Shik Kim1
  • 1Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanaggu, Seou, South Korea
Further Information

Publication History

received 11 January 2017
revised 07 March 2017

accepted 09 March 2017

Publication Date:
13 June 2017 (online)

Abstract

Cis-trans isomers of N 1,N 5,N 9,N 14-tetra-p-coumaroyl thermospermines and N 1,N 5,N 10,N 14-tetra-p-coumaroyl spermines were found in Matricaria chamomilla, German chamomile using countercurrent chromatography with methylene chloride-methanol-water (1:1:1, v/v/v). Their structures were elucidated based on spectroscopic and spectrometric data (1D and 2D NMR, and HRESIMS). The antagonistic activity against the neurokinin-1 receptor was examined by a calcium assay, measuring the cytosolic fluorescence triggered by substance P binding to the receptor. The compounds 1a/1b, 2a/2b, and 3a/3b potently suppressed the calcium flux compared to the known antagonist L-703,606 oxalate, indicating that the compounds competitively inhibited the binding of substance P. They also suppressed substance P-induced proliferation in MDA-MB-453, the HER2-amplified breast cancer cell line. It is suggested that tetracoumaroyl thermospermines and tetracoumaroyl spermines are promising antagonists, exerting positive effects on substance P/neurokinin-1 receptor-related diseases.

Supporting Information