Caffeate and piperidine-3-ol derivatives from the stem bark of Cassia sieberiana.

A new caffeate derivative from the ethanol extract of the stem bark of Cassia sieberiana DC. is described herein along with the known secondary metabolites spectaline (2), iso-6-cassine (3), 3-O-methyl-chiro-inositol (4), monobehenin (5), octyl nonadecyloate (6), ß-sitosterol (7), stigmasterol (8) and sitosterol 3-O-ß-D-glucopyranoside (9). The chemical structures were elucidated by means of various spectroscopic and spectrometric techniques. Extract and isolated compounds were devoid of inhibitory action against the herein selected bacterial strains (MICs > 256 µg/mL) but showed capacities to reduce 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (EC50 < 3 µg/mL) considerably better than the "gold standard" trolox (EC50 6.47 ± 0.48 µg/mL).

A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death.

INTRODUCTION: Multidrug resistance of cancer cells constitutes a serious problem in chemotherapy and a challenging issue in the discovery of new cytotoxic drugs. Many saponins are known to display anti-cancer effects. In this study, the cytotoxicity and the modes of action of a naturally occuring oleanane-type tritepene saponin, ardisiacrispin B isolated from the fruit of Ardisia kivuensis Taton (Myrsinaceae) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant phenotypes. METHODS: Resazurin reduction assay was used to evaluate cytotoxicity and ferroptotic cell death of samples; caspase-Glo assay was used to detect the activation of caspases in CCRF-CEM leukemia cells. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells by annexin V/PI staining, analysis of mitochondrial membrane potential (MMP) and measurement of reactive oxygen species (ROS). RESULTS: Ardisiacrispin B displayed significant cytotoxic effects in the 9 tested cancer cell lines with IC50 values below 10 µM. The IC50 values ranges were 1.20 µM (towards leukemia CCRF-CEM cells) to 6.76 µM [against heptocarcinoma HepG2 cells] for ardisiacrispin B and 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against resistant CEM/ADR5000 leukemia cells) for doxorubicin. Collateral sensitivity of resistant HCT116p53-/- colon adenocarcinoma cells to ardisiacripsin B was observed. Ardisiacrispin B induced apoptosis in CCRF-CEM cells via activation of inititator caspases 8 and 9 and effector caspase 3/7, alteration of MMP and increase in ROS production. Ferroptosis also contributed to the cytotoxicity of ardisiacrispin B. CONCLUSIONS: The studied oleanane-type triterpene saponin is a good cytotoxic molecule that deserve more detailed exploration in the future, to develop novel cytotoxic drugs to combat both sensitive and drug-resistant cancers.

A New Alkenylmethylresorcinol from the Fruits of Ardisia kivuensis.

The phytochemical study of the MeOH extract from the fruits of Ardisia kivuensis was carried out using repeated silica gel column chromatography followed by Sephadex LH-20 to afford a new alkenylmethylresorcinol, ardisinol III (1) along with three known compounds, oleanolic acid, ß-sitosterol and pentacosanoic acid. The structure of 1 was elucidated using spectroscopic analysis (NMR and MS), and comparison with published data. Compound 1 had weak antioxidant activity (IC50 109.8 µg/mL) while other compounds were not active as compared to L-ascorbic acid (IC50 3.9 µg/mL).

Ardisikivuoside, a new triterpenoid saponin from Ardisia kivuensis (Myrsinaceae).

Column chromatography of the n-butanol extract of the stem of Ardisia kivuensis (Myrsinaceae) led to the isolation of a new triterpenoid saponin, ardisikivuoside (1) {3-O-beta-D-xylopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1 --> 4)-beta-D-xylopyranosyl-3beta-hydroxy-13beta,28-epoxyoleanan-16-oxo-30-al}. The structure was elucidated on the basis of spectral studies.