A convenient preparation of a disaccharide motif and its role in the cytotoxicity of the triterpenoid saponin, α-hederin

Abstract

The sugar structures of triterpenoid saponins, such as alpha-hederin, are intimately associated with their antitumor activities and other biological activities. The alpha-L: -rhamnopyranosyl-(1-->2)-alpha-L: -arabinopyranoside group of alpha-hederin alters the cytotoxicity of its aglycon, hederagenin. This study explored the role of this saccharide unit in the cytotoxic effect of alpha-hederin and the possibility of its use as a carrier moiety in prodrugs of anticancer agents. A new convenient and practical procedure for the preparation of 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-alpha-L: -rhamnopyranosyl-(1-->2)-3,4-O-dibenzoyl-beta-L: -arabinopyranoside (2) from 4-methoxybenzoyl-beta-L: -arabinopyranoside was accomplished using four steps with an overall yield of 63%. The use of BF(3)-OEt(2) as a catalyst in the glycosylation step in this procedure had a large advantage over the TMSOTf catalyst used in the usual method. Moreover, the key intermediate obtained in this procedure, 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-alpha-L: -rhamnopyranosyl-(1-->2)-alpha-L: -arabinopyranoside (7), was selectively transformed to 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-alpha-L: -rhamnopyranosyl-(1-->2)-4-O-acetyl-alpha-L: -arabinopyranoside (9) and 4-methoxybenzoyl-2,3,4-tri-O-benzoyl-alpha-L: -rhamnopyranosyl-(1-->2)-3-O-benzoyl-beta-L: -arabinopyranoside (10). These derivatives did not show any cytotoxicity against human cancer cell lines. Thus the 3-O-alpha-L: -rhamnopyranosyl-(1-->2)-alpha-L: -arabinopyranoside could be used as a nontoxic carrier moiety to enhance the activity of anticancer drugs.

α-hederin induces autophagic cell death in colorectal cancer cells through reactive oxygen species dependent AMPK/mTOR signaling pathway activation

“…With its strong anticancer effect and multiple anticancer mechanisms, α-hederin may potentially become a more reliable anticancer drug. However, due to its strong toxicity (54-57), protein absorption (58) and hemolytic effect (59), further molecular modifications and nanotarget drug carriers should be applied during the anticancer study of α-hederin.…”

Alpha-Hederin, the Active Saponin of Nigella sativa, as an Anticancer Agent Inducing Apoptosis in the SKOV-3 Cell Line

“…To our knowledge, not much information is available about the influence of α-HN on the SKOV-3 ovarian cell line [20] and also no data are available about the mechanism underlying this effect.…”

“…α-HN is also active against other cell lines, for instance: Lewis lung carcinoma (LL/2), smooth muscle (HASM), human kidney (HEK293), and transfected HEK293 cell lines [18,19]. With regard to colon cancer (HT-29), α-HN is claimed to act synergistically with 5-fluorouracil and 3- O -α- l -rhamnopyranosyl-(1→2)-α- l -arabinopyranoside [20,21]. Furthermore, α-HN was also tested in comparison to its chitosan nanoparticles (α-HN-CS-CD147-NPs) on human liver cancer cell lines SMMC-7721 and HepG2 and it was found that the antibody when coupled with α-HN became more active against these cell lines than α-HN alone [22].…”

Naturally Derived Formulations and Prospects towards Cancer

“…Saponin exhibits anti-microbial activity and has a lytic effect on erythrocyte membrane [73]. It has also demonstrated hypoglycemic effect [74] and lowering of serum cholesterol levels in animals [75] [76]. Saponins reduce protein digestibility by the formation of sparingly digestible saponin-protein complexes [77].…”