Some novel alkyl amine-substituted icariside II (ICA II) derivatives were synthesized
Some novel alkyl amine-substituted icariside II (ICA II) derivatives were synthesized by Mannich reactions on the 6-C position (materials 4aCompact disc) and changing the carbon chain length on the 7-OH position (materials 7aCh), and their in vitro antitumor activity towards individual breasts cancer lines (MCF-7 and MDA-MB-231) and individual hepatoma cell lines (HepG2 and HCCLM3-LUC) were evaluated with the MTT assay. from the 7-(Sieb.et Zucc.) Maxim., Maxim., Nakai, Maxim. EF, named yinyanghuo also, barrenwort, copper cable faeries and lawn spleen, and continues to be utilized being a tonic supplement for building up the nourishing and bone fragments the kidneys in East Asia, in China particularly, Japan and Korea, for a large number of years . Icariin (ICA), an 8-isopentenyl flavonoid glycoside (Amount 1, substance A), may be the main substances of EF . ICA possesses a wide-range of pharmacological results, such as for example antidepressant-like, hormone Avasimibe kinase activity assay legislation, anti-inflammatory, neuroprotective, antioxidative, antirheumatic, and antiosteoporotic results [10,11,12,13,14]. Rabbit Polyclonal to RAB18 Furthermore, ICA was reported to demonstrate anticancer activity against some human cancer tumor cell lines. For instance, Zheng et al. discovered that ICA could suppress thyroid carcinoma cell (B-CPAP) proliferation by inducing high appearance of intracellular ROS and reducing the appearance of antioxidase ; ICA could induce apoptosis and arrest cell routine at S stage in medulloblastoma cells to suppress proliferation . Icariside II (ICA II), another active component of EF (Amount 1, substance B), is produced with the intestinal flora from ICA by the increased loss of the glycosyl moiety on the C-7 placement . Our group spent some time working over the advancement of ICA and discovered that 91 extensively.2% of ICA was transformed into ICA II after oral administration, and direct oral administration of ICA II increased its focus in the physical body resulting in faster absorption, slower metabolism and higher absolute bioavailability . Weighed against ICA, ICA II possesses more powerful activity against irritation, osteoporosis, cancers, and improves erection dysfunction [19,20,21,22,23]. We’ve explored the anticancer activity of ICA ICA and II, and the outcomes (see Desk 1) demonstrated that ICA II acquired better anticancer actions than ICA. Hence, ICA II provides attracted increasing analysis interest. However, as the quantity of organic ICA II in EF was about just 0.01% g/g, which is approximately 1/60C1/6 that of ICA, we likewise have optimized biotransformation of ICA into ICA II by -Gglucosidase for even more pharmaceutical research . Open up in another window Amount 1 The buildings of icariin (A) and icariside II (B). Desk 1 Antitumor cell proliferation activity of alkyl amine derivatives of ICA II by MTT assay. = 3 for even more study. With the perfect linker at hand, we prepared to present different terminal amine substituents to research the possible results on anticancer activity. Using a cyclic amine group Avasimibe kinase activity assay (a morpholinyl or pyrrolidyl group) on the terminal placement of 7-(4a). Produce 70%; yellowish solid; m.p. 80.0C81.8 C; ESI/MS = 8.7 Hz, 2H), 7.02 (d, = 8.8 Hz, 2H), 5.50 (s, 1H), 5.32 (s, 1H), 5.22 (s, 1H), 3.88 (s, 3H), 3.84 (s, 2H), 3.62 (m, 7H), 3.48C3.42 (m, 2H), 3.31 (dd, = 13.7, 7.6 Hz, 1H), 2.41 (s, 6H), 1.76 (s, 3H), 1.70 (s, 3H). 13C-NMR (100 MHz, CDCl3) 178.4, 164.1, 161.7, 157.1, 156.7, 153.8, 134.9, 131.8, 130.6, 130.6, 123.0, 122.6, 114.0, 114.0, 106.5, 104.2, 103.4, 101.7, 72.5, 71.5, 70.60, 70.3, 55.5, 50.9, 44.1, 44.1, 25.8, 18.0, 17.1. (4b). Produce 79%; yellowish solid; m.p. 155.0C157.1 C; ESI/MS = 8.7 Hz, 2H), 7.02 (d, = 8.7 Hz, 2H), 5.50 (s, 1H), 5.24 (s, 1H), 4.46 (s, 1H), 3.94 (m, 2H), 3.91 (m, 6H), 3.88 (s, 3H), 3.46 (m, 3H), 3.35C3.24 (m, 1H), 2.73 (dd, = 14.0, 6.9 Hz, 4H), 1.75 (s, 3H), 1.70 (s, 3H), 1.17 (t, = 7.1 Hz, 6H). 13C-NMR (100 MHz, CDCl3) 178.3, Avasimibe kinase activity assay 161.9, 161.6, 157.0, 156.6, 153.8, 134.8, 131.6, 130.6, 130.6, 123.1, 122.7, 113.9, 113.9, 106.6, 103.4, 103.5, 101.6, 72.5, 71.6, 70.6, 70.2, 55.5, 49.1, 46.4, 46.4, 25.8, 18.0, 17.1, 10.8, 10.8. (4c). Produce 85%; Avasimibe kinase activity assay yellowish solid; m.p. 115.7C116.5 C; ESI/MS = 8.7 Hz, 2H), 7.02 (d,.