Synthetic Secofriedelane and Friedelane Derivatives as Inhibitors of Human Lymphocyte Proliferation and Growth of Human Cancer Cell Lines in Vitro

Abstract

Controlled silylation of friedelin (1) from cork smoker wash solids, a byproduct generated during processing of corkboard by steam baking, gave 3-trimethylsiloxyfriedel-2-ene (3) in high yields. Oxidation of 3 with OsO(4)/NMMO produced 2alpha-hydroxyfriedelan-3-one (cerin) (5), from which the new 2,3-secofriedelan-2-al-3-oic acid (6) was obtained quantitatively by periodic acid oxidation. Oxidation of 3 with DDQ afforded friedel-1-en-3-one (8). Reductive ozonolysis of 3 gave 2alpha,3beta-dihydroxyfriedelane, pachysandiol A (7). Compound 6 proved to be a potent inhibitor of human lymphocyte proliferation (IC(50) = 10.7 microM) and of the growth of a human cancer cell line (GI(50) = 5.4-17.2 microM). (13)C NMR data for compounds (3, 4, 5, 6a,7, and 8) are described for the first time.

Evaluation of the proliferative activity of methanol extracts from six medicinal plants in murine spleen cells

“…Although triterpenes and flavonoids have been described in the literature as inhibitors of human lymphocytes proliferation (Moiteiro et al, 2001;Brochado et al, 2003;Arokiyaraj et al, 2007), the action of these compounds appears to be inhibited by other compounds with immunostimulating effects, such as alkaloids (Sheng, Bryngelsson, Pero, 2000), since the results obtained showed an increase in cell proliferation and possibly activation of T lymphocytes. Given the finding of the stimulating lymphocyte response and that the literature describes the betulinic acid, also present in this species, as a promising anticancer agent against melanoma by inhibiting the growth of cancer cells and inducing apoptosis (Pettit, 1996), the continuity of studies with fractions and isolated compounds of this plant can contribute to advances in the field of immunotherapy.…”

“…For instance, the gallic acid present in other species prevents DNA oxidation, preventing cell death by accumulation of nitric oxide in the culture medium (Kuhlmann et al, 1998). The coumarin extracted from Hydrangeae dulcis folium had no effect on the response of human T lymphocytes stimulated with PHA (Shimoda et al, 1998), while triterpenes from the bark of Quercus suber proved a potent inhibitor of human lymphocyte proliferation, as well as reducing the growth of the human cancer cell strain (Moiteiro et al, 2001). Triterpenes isolated from the leaves of Justicia gendarussa also showed inhibition of human lymphocyte proliferation, with maximum inhibition of 85%,when using a methanol extract of the plant (Arokiyaraj et al, 2007).…”

“…Although the coumarins extracted from other medicinal plants have shown no influence on the proliferation of human lymphocytes (Shimoda et al, 1998) whereas flavonoids and triterpenes inhibited the proliferation of these cells (Patocka, 2003;Moiteiro et al, 2001;Reyes et al, 2006;Arokiyaraj et al, 2007), betulin, another compound present in M. elaeagnoides, has shown mitogenic activity and the ability to induce and modulate cytokine production in cultured human cells (Zdzisińska et al, 2003).…”

“…The triterpene friedelin appears to be the main component responsible for the action of this species against ulcers and gastritis, while in other plants it has been associated to inhibition of human lymphocyte proliferation (Moiteiro et al, 2001;Arokiyaraj et al, 2007). The presence of this triterpene in M. robusta suggests that the biological activity of this compound is predominant over other compounds in the murine spleen cell culture.…”

Pre-treatment and extraction techniques for recovery of added value compounds from wastes throughout the agri-food chain

“…[173][174][175][176][177][178][179][180][181][182] These molecules can be utilised in a wide array of applications including cosmetics, cleaning products, flavour and fragrance, insecticides, degreasers, lubricants, nutraceuticals and pharmaceuticals. [183][184][185][186][187][188][189][190][191][192][193] ScCO 2 wax fractions from corn stover were found to be effective as anti-foaming agents in detergent formulations, which could be a potential replacement for the current non-renewable anti-foams that are widely known to have a number of negative impacts, such as eutrophication ( phosphates), carcinogenic products, and persistence in the environment (silicates). 177,194 Recent work has demonstrated the economic viability of scCO 2 extraction of corn stover wax, with the lowest cost of production found to be €4.56 per kg of wax.…”