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Cancer is the major public health problem worldwide; consequently, the search for new chemotherapeutic drugs is constant. Most of these agents are derived from natural sources, which are the major consistent basis for the search for modern anticancer medicines. In this context, numerous studies indicate flavonoids as a potential new class of secondary metabolites for anticancer therapy. In this review, special attention was addressed to flavonoids present in Achyrocline satureioides, a widely used medicinal plant with several and a well established range of biological properties. Two of these flavonoids are extensively studied for anticancer therapy, quercetin and luteolin, followed by 3-Omethylquercetin. Achyrobichalcone, recently isolated from A. satureioides by our group, can also represent a promising chemotherapeutic biomolecule due to its similarity with other cytotoxic bichalcones to cancer cell lines. The anticancer properties of these flavonoids, specially quercetin and luteolin, type of cell death, mechanisms and molecular targets involved were described. In general, these effects were observed due to the inhibition of cell proliferation, cell cycle arrest, apoptosis, inhibition of angiogenesis, prevention of migration/metastasis and overcoming multidrug resistance, alone or in combination with commonly used chemotherapeutic drugs. All these successful findings in preclinical studies suggest that these flavonoids are promising biomolecules for the development of new anticancer drugs in the future.

Achyrobichalcone is a biflavonoid recently found in Achyrocline satureioides. This substance has unprecedented chemical structure and occurrence, but resembles other bioactive bichalcones, which have important pharmacological properties, such as anticancer activity. The major challenge for evaluation of the physicochemical and biological properties of this new molecule is the isolation step, which affects the purity and yield of the isolated product. Thus, the objective of this work was to develop a semi-preparative method for achyrobichalcone isolation from Achyrocline satureioides by high-speed countercurrent chromatography. The high-speed countercurrent chromatography separation was achieved in two steps. In the first step, an enriched fraction of achyrobichalcone from the freeze-dried extract was obtained, using the solvent system hexane-ethyl acetate-methanol-water 0.8:1:0.8:1, v/v. The purification of achyrobichalcone from the enriched fractions was achieved by further high-speed countercurrent chromatography fractionation with hexane-ethyl acetate-methanol-water 0.9:0.9:0.8:1, v/v. The final isolated product was obtained using preparative thin layer chromatography and crystallization procedure. A yellow semi-crystalline solid with purity close to 90% was obtained as the final product. The mass recovery of achyrobichalcone isolation was near 67%. The structural identification from spectroscopic and chromatographic techniques confirmed the achyrobichalcone structure. This is the first report of achyrobichalcone isolation on a semi-preparative scale by high-speed countercurrent chromatography. This method afforded achyrobichalcone in good yield and purity for further biopharmaceutical studies.

The new method developed affords evaluation of the quality of achyrobichalcone obtained by isolation, and indicates the stability of the molecule under various stress conditions.

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Achyrocline satureioides (AS, family Asteraceae) is a plant widely used in traditional medicine for stomach, digestive, and gastrointestinal disorders during pregnancy. Studies regarding the indiscriminate use of plant infusions during pregnancy are limited. Recent reports have shown that chronic flavonoid supplementation induces toxicity in vivo and raises the mortality rates of healthy subjects. Therefore, we investigated whether supplementation of pregnant and lactating Wistar rats with two AS inflorescence extracts, consisting of an aqueous (AQ) extract similar to a tea (47 mg·kg−1·day) and a hydroethanolic (HA) extract (35 mg·kg−1·day−1) with a higher flavonoid content, could induce redox-related side effects. Total reactive antioxidant potential (TRAP), thiobarbituric reactive species (TBARS), and total reduced thiol (SH) content were evaluated. Superoxide dismutase (SOD) and catalase (CAT) activities were additionally quantified. Our data suggest that both AQ and HA of AS inflorescence extracts may induce symptoms of toxicity in concentrations of (47 mg·kg−1·day) and (35 mg·kg−1·day−1), respectively, in mothers regarding the delivery index and further decrease of neonatal survival. Of note, significant tissue-specific changes in maternal (liver, kidney, heart, and hippocampus) and pups (liver and kidney) biochemical oxidative parameters were observed. Our findings provide evidence that may support the need to control supplementation with the AQ of AS inflorescence extracts during gestation due to potential toxicity in vivo, which might be related, at least in part, to changes in tissue-specific redox homeostasis and enzymatic activity.

Over the years, thalidomide has been prescribed for an increasing number of diseases, including multiple myeloma and erythema nodosum leprosum. In Brazil and other countries, thalidomide is available in tablets, and there is no official dissolution testing available for this dosage form. Considering this, a dissolution method was developed and validated for tablets containing 100 mg of each polymorph using 1-L vessels to verify that it can differentiate between polymorphs, since drug product is supposed to be formulated with the α form. In addition, the possibility of using smaller volumes of dissolution medium was also explored.This method was compared with the USP dissolution method for thalidomide capsules (4-L vessel) with independent models using difference and similarity factors as well as dissolution efficiency. Dissolution kinetics was evaluated using zero-order, first-order, Higuchi, and Korsmeyer-Peppas models. The kinetic parameters and the suitability of the models for experimental data were evaluated. The developed dissolution method was fully validated. It allowed a better discrimination of thalidomide polymorphs than the USP method for the formulations tested. Considering that it uses a conventional dissolution apparatus with 1-L vessels and there is no method described for tablets, it can be used for quality control of thalidomide in this dosage form.

Flavonoids from Achyrocline satureioides: Promising Biomolecules for Anticancer Therapy -[178 refs.]. -(CARINI*, J. P.; KLAMT, F.; BASSANI, V. L.; RSC Adv. 4 (2014) 7, 3131-3144, http://dx.doi.org/10.1039/c3ra43627f ; Fac. Farm., Univ. Fed. Rio Grande do Sul, Porto Alegre, 90610 Rio Grande do Sul, Brazil; Eng.) -M. Paetzel 36-276