Alkaloids from Pachysandra terminalis Inhibit Breast Cancer Invasion and Have Potential for Development As Antimetastasis Therapeutic Agents

Abstract

The aim of the present study was to identify potentially useful natural compounds for the development of novel therapeutic agents to inhibit metastasis. A phytochemical investigation of Pachysandra terminalis resulted in the isolation of seven new pregnane alkaloids, terminamines A-G (1-7), and seven known alkaloids (8-14). The structures of 1-7 were elucidated by 1D- and 2D-NMR spectroscopic and mass spectrometric methods. Compounds 1-5 and 8-14 inhibited the migration of MB-MDA-231 breast cancer cells induced by the chemokine epithelial growth factor. In addition, compound 1 inhibited phosphorylation of integrin β(1), which plays an important role in MB-MDA-231 cell adhesion and metastasis.

Terminamines K–S, Antimetastatic Pregnane Alkaloids from the Whole Herb of Pachysandra terminalis

“…The 1 H-NMR spectrum of 2 featured four tertiary methyl signals at δ H 2.04, 1.70, 0.75, and 0.65 (each 3H, s), a secondary methyl at δ H 0.90 (3H, d, J = 6.4 Hz), and six N(CH 3 ) 2 protons at δ H 2.21 (6H, s). The 13 C-NMR spectroscopic data for 2 were similar to those of terminamine E [7], except for the signals of C-4 (Table 1), and 2 was deduced to be the 4-oxo derivative of terminamine E. In the HMBC spectrum, two methyl groups (δ H 2.04 and 1.70) showed a correlation with double bond carbons (δ C 130.9 and 135.1), while the proton signals at δ H 3.93 and 3.68 (H-4 ) showed correlations with δ C 130.9 (C=C) and δ C 165.1 (C=O), suggesting a 3 -isopropylidene lactam. On the other hand, the proton signals at δ H 4.42 (H-3) correlated with signals at δ C 27.6 (C-2), 207.6 (C-4), 45.8, and 165.1 (β-lactam moiety).…”

“…Analysis of the 1 H-and 13 C-NMR data supported a pregnane skeleton in 3 (Table 2), and resembled those of epipachysamine E [7,10] Table 2. NMR Spectroscopic data (400 MHz, CDCl 3 ) for Terminamine M-P (3-6).…”

“…Alkaloid 1 was obtained as a yellow oil and its molecular formula was established as C 38 21 carbon signals were assigned to the pregnane skeleton, similar to those of terminamine C [7]. By comparison of the NMR spectroscopic data with 10, 1 was proposed to have an acetyl group at the C-4 position, instead of a hydroxyl group.…”

“…Previous pharmacological research has shown that these compounds produce a wide range of pharmacological effects, such as antiulcer [4], cytotoxic [3], anti-leishmanial [5], anti-cancer [6], anti-breast cancer metastatic activities [7,8], as well as estrogen biosynthesis-promoting effects [9]. As part of an ongoing research program to identify bioactive steroidal alkaloids with anti-metastatic effects nine new (1)(2)(3)(4)(5)(6)(7)(8)(9) and eight known (10)(11)(12)(13)(14)(15)(16)(17) pregnane alkaloids were isolated from the whole herb of Pachysandra terminalis. The isolation, structure elucidation, and anti-metastatic effects of these compounds are described, and their structure-activity relationships is discussed.…”

Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives

“…) . In addition to their different bio‐potentialities, including analgesic, antimicrobial, and anti‐inflammatory activities, their anticancer potentials are being explored . Numerous synthetic routes have also been developed for synthesizing SA analogs to achieve desired biological effects.…”