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

Sait Byul Park; Kwangho Song; Yeong Shik Kim

doi:10.1055/s-0043-106742

Planta Medica International Open, Table of Contents

CC BY-NC-ND 4.0 · Planta Medica International Open 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 Park

¹Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanaggu, Seou, South Korea

,

Kwangho Song

¹Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanaggu, Seou, South Korea

,

Yeong Shik Kim

¹Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanaggu, Seou, South Korea

› Author Affiliations

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.

Key words

Matricaria chamomilla - Asteraceae - countercurrent chromatography - tetracoumaroyl thermospermines - tetracoumaroyl spermines - NK₁ receptor antagonists - calcium assay

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References

References
1 Srivastava JK, Shankar E, Gupta S. Chamomile: A herbal medicine of the past with bright future. Mol Med Rep 2010; 3: 895-901
2 Kobayashi Y, Nakano Y, Inayama K, Sakai A, Kamiya T. Dietary intake of the flower extracts of German chamomile (Matricaria recutita L.) inhibited compound 48/80-induced itch-scratch responses in mice. Phytomedicine 2003; 10: 657-664
3 Singh O, Khanam Z, Misra N, Srivastava MK. Chamomile (Matricaria chamomilla L.): An overview. Pharmacog Rev 2011; 5: 82-95
4 Yamamoto A, Nakamura K, Furukawa K, Konishi Y, Ogino T, Higashiura K, Yago H, Okamoto K, Otsuka M. A new nonpeptide tachykinin NK1 receptor antagonist isolated from the plants of Compositae. Chem Pharm Bull 2002; 50: 47-52
5 Li WC, Wang XY, Lin PC, Hu N, Zhang QL, Suo YR, Ding CX. Preparative separation and purification of four cis-trans isomers of coumaroylspermidine analogs from safflower by high-speed counter-current chromatography. J Chromatogr B 2013; 938: 75-79
6 Ohta S, Fujimaki T, Uy MM, Yanai M, Yukiyoshi A, Hirata T. Antioxidant hydroxycinnamic acid derivatives isolated from Brazilian bee pollen. Nat Prod Res 2007; 21: 726-732
7 Kakehi JI, Kuwashiro Y, Niitsu M, Takahashi T. Thermospermine is required for stem elongation in Arabidopsis thaliana. Plant Cell Physiol 2008; 49: 1342-1349
8 Fuell C, Elliott KA, Hanfrey CC, Franceschetti M, Michael AJ. Polyamine biosynthetic diversity in plants and algae. Plant Physiol Biochem 2010; 48: 513-520
9 Pegg AE, Michael AJ. Spermine synthase. Cell Mol Life Sci 2010; 67: 113-121
10 Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nature Rev Mol Cell Biol 2000; 1: 11-21
11 Yip J, Chahl LA. Localization of NK1 and NK3 receptors in guinea-pig brain. Regul Pept 2001; 98: 55-62
12 Ebner K, Singewald N. The role of substance P in stress and anxiety responses. Amino Acids 2006; 31: 251-272
13 Seto S, Tanioka A, Ikeda M, Izawa S. Design and synthesis of novel 9-substituted-7-aryl-3,4,5,6-tetrahydro-2H-pyrido(4,3-b)- and (2,3-b)-1,5-oxazocin-6-ones as NK1 antagonists. Bioorg Med Chem Lett 2005; 15: 1479-1484
14 Otsuka M, Yoshioka K, Yanagisawa M, Suzuki F, Zhao FY, Guo JZ, Hosoki R, Kurihara T. Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A. Can J Physiol Pharmacol 1995; 73: 903-907
15 Muñoz M, Rosso M, Coveñas R. The NK-1 receptor: a new target in cancer therapy. Curr Drug Targets 2011; 12: 909-921
16 Muñoz M, Rosso M, Covenas R. A new frontier in the treatment of cancer: NK-1 receptor antagonists. Curr Med Chem 2010; 17: 504-516
17 Singh D, Joshi DD, Hameed M, Qian J, Gascon P, Maloof PB, Mosenthal A, Rameshwar P. Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis. Proc Natl Acad Sci USA 2000; 97: 388-393
18 Rao G, Patel PS, Idler SP, Maloof P, Gascon P, Potian JA, Rameshwar P. Facilitating role of preprotachykinin-I gene in the integration of breast cancer cells within the stromal compartment of the bone marrow: A model of early cancer progression. Cancer Res 2004; 64: 2874-2881
19 Mayordomo C, Garcia-Recio S, Ametller E, Fernandez-Nogueira P, Pastor-Arroyo EM, Vinyals L, Casas I, Gascon P, Almendro V. Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2. J Cell Physiol 2012; 227: 1358-1366
20 Garcia-Recio S, Fuster G, Fernandez-Nogueira P, Pastor-Arroyo EM, Park SY, Mayordomo C, Ametller E, Mancino M, Gonzalez-Farre X, Russnes HG, Engel P, Costamagna D, Fernandez PL, Gascón P, Almendro V. Substance P autocrine signaling contributes to persistent HER2 activation that drives malignant progression and drug resistance in breast cancer. Cancer Res 2013; 73: 6424-6434
21 Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res 2011; 13: 1-7

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