Flavonolignans: One Step Further in the Broad-Spectrum Approach of Cancer.

BACKGROUND: The small chemical class of flavonolignans encompasses unique hybrid molecules with versatile biological activities. Their anticancer effects have received considerable attention, and a large body of supporting evidence has accumulated. Moreover, their ability to interact with proteins involved in drug resistance, and to enhance the effects of conventional chemotherapeutics in decreasing cell viability make them influential partners in addressing cancer. OBJECTIVE: The review provides an outline of the various ways in which flavonolignans advance the combat against cancer. While the main focus falls on flavonolignans from milk thistle, attention is drawn to the yet, underexplored potential of less known flavonolignan subgroups derived from isoflavonoids and aurones. METHODS: Proceeding from the presentation of natural flavonolignan subtypes and their occurrence, the present work reviews these compounds with regard to their molecular targets in cancer, anti-angiogenetic effects, synergistic efficacy in conjunction with anticancer agents, reversal of drug resistance, and importance in overcoming the side effects of anticancer therapy. Recent advances in the endeavor to improve flavonolignan bioavailability in cancer are also presented. CONCLUSIONS: Significant progress has been achieved in detailing the molecular mechanisms of silybin and its congeners in experimental models of cancer. The availability of novel formulations with improved bioavailability, and data from phase I clinical trials in cancer patients provide an encouraging basis for more extensive trials aimed at evaluating the benefits of Silybum flavonolignans in cancer management. On the other hand, further research on the antitumor efficacy of iso-flavonolignans and other subtypes of flavonolignans should be pursued.

Cotinus coggygria wood: novel flavanone dimer and development of an HPLC/UV/MS method for the simultaneous determination of fourteen phenolic constituents.

Phytochemical investigations of Cotinus coggygria Scop. wood, a medicinal and tinctorial plant used since antiquity, resulted in the isolation and structure elucidation of the novel C-3/C-3'' dimer of butin (3',4',7-trihydroxyflavanone) and other known compounds: gallic acid and its methyl ester; catechin; profisetinidins: fisetinidol-(4α→8)-(+)-catechin and epifisetinidol-(4ß→8)-(+)-catechin; flavanonols: fustin and dihydroquercetagetin; flavanones: butin and eriodictyol; flavonols: fisetin and quercetin; the chalcone butein and the aurone sulfuretin. The isolated compounds were used for the development and validation of a HPLC-method which enables the determination of these bioactive substances in C. coggygria extracts. Separation was possible on an ether-linked phenyl column material, using as mobile phase mixtures of water, methanol, and acetonitrile with 0.02% trifluoroacetic acid. Sensitivity, selectivity, linearity, precision, accuracy, and repeatability of the method were verified and assured suitability for its intended use. LC-MS experiments performed in positive and negative electrospray ionization mode confirmed the identity of analytes and allowed unambiguous assignment of all peaks of interest. The analysis of different C. coggygria samples revealed that sulfuretin (0.38-0.69%) and fustin (0.33-0.59%) dominated, followed by dihydroquercetagetin (0.12-0.35%), a rare flavanonol derivative with a 5,6,7-trihydroxysubstituted A-ring. The new natural compound C-3/C-3'' flavanone dimer occurred in concentrations of 0.03-0.06%; the two latter compounds could represent valuable markers for the identification and quality control of C. coggygria wood.