Vakhtang Mshvildadze

Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins.

The haemolysis of red blood cells inducing toxicity in most animals including humans is a major drawback for the clinical development of saponins as antitumour agents. In this study, the haemolytic and cytotoxic activities as well as the membrane cell permeabilization property of a library of 31 semi-synthetic and natural lupane- and oleanane-type saponins were evaluated and the structure-activity relationships were established. It was shown that lupane-type saponins do not exhibit any haemolytic activity and membrane cell permeabilization property at the maximum concentration tested (100 microM) independently of the nature of the sugar moieties. While oleanane-type saponins such as beta-hederin (25) and hederacolchiside A(1) (27) cause the death of cancer cell lines by permeabilizing the cellular membranes, lupane-type saponins seem to proceed via another mechanism, which could be related to the induction of apoptosis. Altogether, the results indicate that the cytotoxic lupane-type glycosides 10 and 22 bearing an alpha-l-rhamnopyranose moiety at the C-3 position represent promising antitumour agents for further studies on tumour-bearing mice since they are devoid of toxicity associated with the haemolysis of red blood cells.

Cytotoxic activity of withanolides isolated from Tunisian Datura metel L.

Withanolide-type steroids, withametelin Q (1) and 12α-hydroxydaturametelin B (2) along with three known withanolides, were isolated from leaves of Datura metel L. (Solanaceae). The respective structures, characterized mainly by NMR spectroscopy, were identified as (20R,22R,24R)-21,24-epoxy-1α,3β-dihydroxywitha-5,25(27)-dienolide-3-O-β-D-glucopyranoside (1) and (20R,22R,24R)-12α,21,27-trihydroxy-1-oxowitha-2,5,24-trienolide-27-O-β-D-glucopyranoside (2). The cytotoxicity of isolated compounds was evaluated against human lung carcinoma cells (A549) and human colorectal adenocarcinoma cells (DLD-1), respectively. Compound 2 exhibited cytotoxicity against A549 and DLD-1 cell lines, with IC50 values of 7 and 2.0 μM, respectively. However, for compounds 6 and 7, cytotoxicities were higher against DLD-1 cells with IC(50) values of 0.6 and 0.7 μM. Both compounds blocked the cell cycle in the S-phase and induced apoptosis.

Antioxidant and anti-inflammatory activities of quercetin 7-O-β-D-glucopyranoside from the leaves of Brasenia schreberi.

Brasenia schreberi Gmel. (Cabombaceae) is an aquatic plant that grows in eastern Asia, Australia, Africa, and North and Central America. B. schreberi leaf extracts were obtained by sequential solvent extraction with dichloromethane, methanol, and water. The antioxidant potential of each extract was assessed by using the oxygen radical absorbance capacity (ORAC) assay. With this method, methanol and water extracts were found to be active with mean ± standard deviation values of 7 ± 2 and 5.1 ± 0.5 μmol Trolox® equivalents (TE)/mg, respectively. Two major phenolic compounds, quercetin-7-O-β-D-glucopyranoside and gallic acid, were respectively isolated from the methanolic and water extracts. Both compounds exhibited antioxidant activities, in particular quercetin-7-O-β-D-glucopyranoside (ORAC value, 18 ± 4  μmol TE/μmol). In contrast to its well-known antioxidant homologue quercetin, quercetin-7-O-β-D-glucopyranoside does not inhibit growth of human fibroblasts (WS-1) or murine macrophages (RAW 264.7). Some flavonoids have been reported to possess beneficial effects in cardiovascular and chronic inflammatory diseases associated with overproduction of nitric oxide. Quercetin-7-O-β-D-glucopyranoside possesses anti-inflammatory activity, inhibiting expression of inducible nitric oxide synthase and release of nitric oxide by lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. Quercetin-7-O-β-D-glucopyranoside also inhibited overexpression of cyclooxygenase-2 and granulocyte macrophage-colony-stimulating factor.

Isolation and identification of cytotoxic compounds from the wood of Pinus resinosa

Methanol extracts of wood from Pinus resinosa were found to be selectively cytotoxic against human lung carcinoma cells, A549 (IC50 41 ± 6 µg/mL), human colorectal adenocarcinoma cells, DLD‐1 (IC50 47 ± 4 µg/mL) in comparison with healthy cells, WS1 (IC50 130 ± 11 µg/mL). Five known compounds were isolated and identified by 1H, 13C NMR spectroscopy and HR‐ESI‐MS mass spectrometry as, pinosylvin monomethyl ether (1), pinosylvin (2), pinosylvin dimethyl ether (3), pinobanksin (4) and (‐)‐norachelogenin (5). Compound 4 was isolated for the first time in P. resinosa. The cytotoxicity of compounds 1–5 was evaluated against A549, DLD‐1 and WS1. Compound 1 exhibited the strongest cytotoxicity against both tumor cell lines and the healthy cell line with an IC50 of 25 ± 4 µm for A549, 20 ± 1 µm for DLD‐1 and 34 ± 3 µm for WS1. Copyright

Cytotoxic Steroidal Saponins from the Flowers of Allium leucanthum

Allium leucanthum C. Koch is an endemic Caucasian species that grows in Georgia. The flowers are used in traditional medicine. Phytochemical investigation allowed the isolation of seven spirostanol type saponins from the flowers. Their structures were elucidated on the base of NMR and HRESIMS spectrometry data. A new compound, which we have named leucospiroside A (5), has been identified as (25R)-5α-spirostane-2α,3β,6β-triol 3-O-β-glucopyranosyl-(1→3)-β-glucopyranosyl-(1→2)-[β-glucopyranosyl-(1→3)]-β-glucopyranosyl-(1→4)-β-galactopyranoside. The six others were known substances, but are described in this plant for the first time. The crude extract, spirostanol and furostanol fractions, as well as isolated compounds, were evaluated for their in vitro cytotoxic activity. Compounds 1-3 and 5 were found to be the most active, with relatively similar IC50 values ranging from 3.7 to 5.8 µM for a lung cancer cell line (A549) and 5.6 to 8.2 µM for a colon cancer cell line (DLD-1).

Abibalsamins A and B, Two New Tetraterpenoids from Abies balsamea Oleoresin

Abibalsamins A (1) and B (2), two unprecedented tetraterpenoids featuring a 3,4-seco-rearranged lanostane system fused with a β-myrcene lateral chain via a [4 + 2] Diels-Alder cycloaddition, were isolated from the oleoresin of Abies balsamea. Their structures were elucidated by means of extensive 2D NMR, IR, and MS spectroscopy analyses. The absolute configuration of 1 was determined by single-crystal X-ray diffraction. Both compounds exhibited significant cytotoxic activity against cancer cell lines.

Lanostane- and cycloartane-type triterpenoids from Abies balsamea oleoresin

Summary Phytochemical analysis of A. balsamea oleoresin led to the isolation of three new 3,4-seco-lanostane triterpenoids 1–3, one new cycloartane triterpenoid 4 along with fourteen known terpenoids. Structure determinations were based on extensive 1D/2D NMR, IR and MS spectroscopic analyses, and comparison with literature data. The isolated compounds were evaluated in vitro for their cytotoxicity against human cell lines (A549, DLD-1, WS1) and their antibacterial activity against E. coli and S. aureus. Abiesonic acid (6) exhibited weak cytotoxic activity against A549 (IC50 = 22 µM) while compounds 1 and 4 were weakly active against S. aureus (MIC = 25 µM).

DFT Calculations and ROESY NMR Data for the Diastereochemical Characterization of Cytotoxic Tetraterpenoids from the Oleoresin of Abies balsamea

Eight non-carotenoid tetraterpenoids, abibalsamins C-J (3-10), were isolated from the oleoresin of Abies balsamea. Their chemical structures were determined based on analysis of 1D/2D NMR and MS data. The assignment of their relative configurations was accomplished using homonuclear coupling constants in tandem with ROESY data. However, the presence of two stereogenic centers on a flexible side chain complicated the characterization. In silico models and ROESY data were analyzed in order to assign relative configurations of the isolated tetraterpenoids. Abibalsamins B and H-J showed moderate cytotoxicity against human A549 lung carcinoma cells, with IC50 values ranging between 6.7 and 10 μM.

Antibacterial Balsacones J-M, Hydroxycinnamoylated Dihydrochalcones from Populus balsamifera Buds.

A phytochemical investigation of buds from the hardwood tree Populus balsamifera led to the isolation of six new cinnamoylated dihydrochalcones as pairs of racemates and one as a racemic mixture along with the known compound iryantherin-D (2), the absolute configuration of which was determined for the first time. The structures of balsacones J (1), K (3), L (4), and M (5) were elucidated on the basis of spectroscopic data (1D and 2D NMR, IR, and MS). Chiral HPLC separations were carried out, and the absolute configuration of the isolated enantiomers unambiguously established via X-ray diffraction analyses and electron circular dichroism spectroscopic data. Each of the purified enantiomers exhibited potent in vitro antibacterial activity against Staphylococcus aureus with IC50 values ranging from 0.61 to 6 μM.

A new flavonol glycoside from the medicinal halophyte Suaeda fruticosa.

A new flavonol glycoside, namely 3-(α-rhamnopyranosyl-(1 → 2)-[β-xylopyranosyl-(1 → 6)]-β-glucopyranosyloxy) isorhamnetin was reported from methanol extracts of aerial parts of Suaeda fruticosa for the first time. In this work, liquid chromatography coupled to atmospheric pressure chemical ionisation mass spectrometry, high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy were used to identify this new compound. Structure was elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC and 1H–1H COSY. Antioxidant potentialities of a pure compound were evaluated. The estimation of antioxidant capacities using oxygen radical absorbance capacity (ORAC method) and a cell based-assay (WS1) indicated that this new flavonol exhibited the highest antioxidant activities with an ORAC value of 5.0 ± 0.3 μmol Trolox/μmol and inhibited the tBH-induced oxidation of 2′,7′-dichlorofluorescin with an IC50 value of 4.9 ± 0.6 μM.