Pyrrolizidine alkaloids and fatty acids from the endemic plant species Rindera umbellata and the effect of lindelofine-N-oxide on tubulin polymerization.

The examination of the aerial parts, roots, and seeds of the endemic plant Rindera umbellata is reported in this paper for the first time. Phytochemical investigation of R. umbellata led to the isolation and characterization of ten pyrrolizidine alkaloids and eleven fatty acids in the form of triglycerides. Pyrrolizidine alkaloids 1-9 were found in the aerial parts, 7 and 8 in the roots, and 6-10, together with eleven fatty acids, in the seeds of this plant species. The structures of compounds 1-10 were established based on spectroscopic studies (¹H- and ¹³C-NMR, 2D NMR, IR and CI-MS). After trans-esterification, methyl esters of the fatty acids were analyzed using GC-MS. The effect of lindelofine-N-oxide (7) on tubulin polymerization was determined.

Isolation and biological evaluation of jatrophane diterpenoids from Euphorbia dendroides.

From the Montenegrin spurge Euphorbia dendroides, seven new diterpenoids [jatrophanes (1-6) and a tigliane (7)] were isolated and their structures elucidated by spectroscopic techniques. The biological activity of the new compounds was studied against four human cancer cell lines. The most effective jatrophane-type compound (2) and its structurally closely related derivative (1) were evaluated for their interactions with paclitaxel and doxorubicin using a multi-drug-resistant cancer cell line. Both compounds exerted a strong reversal potential resulting from inhibition of P-glycoprotein transport.

Optimisation of isolation procedure for pyrrolizidine alkaloids from Rindera umbellata Bunge.

Procedure for isolation of pyrrolizidine alkaloids (PAs) from Rindera umbellata Bunge plant species was optimised. Different extraction media (methanol, ethanol and sulphuric acid), concentration and volume of sulphuric acid, pH of PA solution for alkaline extraction, extraction time and techniques (maceration, ultrasonic and overhead rotary mixer assisted extraction) were investigated. The yields of six PAs (7-angeloyl heliotridane, 7-angeloyl heliotridine, lindelofine, 7-angeloyl rinderine, punctanecine and heliosupine) were monitored by GC-MS/FID. The best results for the isolation all of six PAs were obtained when the extraction was performed with 1 M sulphuric acid (30 mL per 1.00 g of dried sample) by overhead rotary mixer during three days. Optimal pH value for alkaline extraction of PAs with CH2Cl2 was 9, and the extraction should be performed with four portions of 30 mL of CH2Cl2. This procedure could be also useful for a plant sample preparation for GC and LC analyses of PAs.

Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines.

Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Cernjavski & Soska. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo IIα and hif-1α expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1α, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway.

Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines.

Thirteen jatrophane diterpenoids (1-10, 13-15), three previously isolated (11, 12, 16) and a known tigliane (17) were isolated from the latex of Euphorbia dendroides. The structures and relative configurations of compounds were elucidated by spectroscopic techniques. The P-glycoprotein (P-gp) inhibiting activities of the representative set of jatrophanes (1-6 and 11-16) have been assessed. Jatrophanes 2 and 5 demonstrated the most powerful inhibition of P-gp, higher than R(+)-verapamil and tariquidar in colorectal multi-drug resistant (MDR) cells (DLD1-TxR).