Antiproliferative Activity of Two Unusual Dimeric Flavonoids, Brachydin E and Brachydin F, Isolated from Fridericia platyphylla (Cham.) L.G.Lohmann: In Vitro and Molecular Docking Evaluation.

Despite the breakthrough in the development of anticancer therapies, plant-derived chemotherapeutics continue to be the basis of treatment for most types of cancers. Fridericia platyphylla is a shrub found in Brazilian cerrado biome which has cytotoxic, anti-inflammatory, and analgesic properties. The aim of this study was to investigate the antiproliferative potential of the crude hydroethanolic extract, subfraction (containing 59.3% of unusual dimeric flavonoids Brachydin E and 40.7% Brachydin F), as well as Brachydin E and Brachydin F isolated from F. platyphylla roots. The cytotoxic activity was evaluated in glioblastoma, lung, prostate, and colorectal human tumor cell lines. The crude hydroethanolic extract did not present cytotoxic activity, but its subfraction presented lower IC50 values for glioblastoma (U-251) and prostate adenocarcinoma (PC-3) cell lines. Brachydins E and F significantly reduced cell viability, proliferation, and clonogenic potential of PC-3, inducing them to the process of regulated cell death. In silico studies have indicated nuclear receptors as targets for Brachydins E and F, and molecular docking has pointed out their binding into glucocorticoid receptor (GR) ligand pocket. Targeting GR pathway has been described as a therapeutic strategy, especially for prostate cancer. These results suggest that Brachydin E and Brachydin F are promising compounds to be further explored for their antitumor effects.

Investigation of U-251 cell death triggered by flavonoid luteolin: towards a better understanding on its anticancer property against glioblastomas.

Recently, many studies have reported the anticancer properties of flavonoid luteolin against a variety of tumors, but there is still a lack in the description of its mechanism of action. In attempt to better contribute to the literature, we evaluated the antiproliferative activity of luteolin extracted by Fridericia platyphylla in a panel of tumor cell lines representative of six different tissues. Luteolin presented antiproliferative activity for all the assessed tumor cell lines, being glioblastoma the most sensitive one. This compound was able to inhibit U-251 cells migration and tumorigenesis. Besides, luteolin leads U-251 tumor cells to apoptosis death by depolarisation of the mitochondrial membrane, ERK proteins phosphorylation, cleavage of PARP and Caspase 9, further inducing DNA damage by H2AX phosphorylation, which had not yet been described for glioblastomas. Altogether, our results reaffirm luteolin as a potential therapeutic drug.

Antiproliferative Flavanoid Dimers Isolated from Brazilian Red Propolis.

Herein reported are results of the chemical and biological investigation of red propolis collected at the Brazilian Northeast coastline. New propolones A-D (1-4), with a 3-{3-[(2-phenylbenzofuran-3-yl)methyl]phenyl}chromane skeleton; propolonones A-C (5-7), with a 3-[3-(3-benzylbenzofuran-2-yl)phenyl]chromane skeleton; and propolol A (8), with a 6-(3-benzylbenzofuran-2-yl)-3-phenylchromane skeleton, were isolated as constituents of Brazilian red propolis by cytotoxicity-guided assays and structurally identified by analysis of their spectroscopic data. Propolone B (2) and propolonone A (5) display significant cytotoxic activities against an ovarian cancer cell line expressing a multiple drug resistance phenotype when compared with doxorubicin.

Production and characterization of collagenase from a new Amazonian Bacillus cereus strain.

A new collagenase producing a strain of Bacillus cereus, isolated from the pollen of a bee of Amazon Region (Brazil), had its enzyme characterized and the production medium composition and culture conditions enhanced. A two-level design on three factors, namely initial medium pH, the substrate (gelatin) concentration and agitation intensity, allowed identifying the first two variables as the most significant ones, while a central composite design (CCD) was subsequently used to identify their optimal levels. Statistics highlighted maximized collagenolytic activity when substrate concentration and initial medium pH were selected at their highest levels (positive effects), whereas agitation intensity at the lowest (negative effect). Triplicate runs performed under predicted optimal conditions (pH 7.8 and 1.7% gelatin concentration) yielded a collagenolytic activity (305.39 ± 5.15 U) 4.6- to 15-fold those obtained with the preliminary design. The enzyme displayed optimum activity at 45 °C and pH 7.2, was stable over wide ranges of pH values and temperatures (7.2-11.0 and 25-50 °C, respectively) and was strongly inhibited by 10 mM phenylmethylsulphonyl fluoride. The zymogram showed two prominent bands at 50 and 76 kDa. These results are a first attempt to elucidate the features of this new collagenase, its production conditions, and possible scale-up.

Antimicrobial and radical scavenging properties of bovine collagen hydrolysates produced by Penicillium aurantiogriseum URM 4622 collagenase.

A 2(3) full factorial design was used to identify the main effects and interactions of pH, collagen concentration and temperature on the degree of collagen hydrolysis (DH) by collagenase from Penicillium aurantiogriseum URM 4622. Increases in both pH and collagen concentration improved DH, and a positive interaction effect was observed for these variables. On the other hand, temperature had a negative main effect on DH. The maximum value of DH (4.65 µg/mL) was achieved at 7.5 mg/mL collagen concentration, pH 8.0 and 25 °C. The peptide profile showed several peptides with molecular weights lower than 2 kDa and exhibited antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. An antioxidant activity of 84.7 ± 0.24 % towards the radical ABTS• + was obtained with 50 mg/mL hydrolysates. This study demonstrated that collagen hydrolysed by P. aurantiogriseum URM 4622 collagenase possesses interesting antibacterial and antioxidant activities.

Composition of the volatile fraction of a sample of Brazilian green propolic and its phytotoxic activity.

BACKGROUND: Propolis is a resinous material produced by honeybees, containing mainly beeswax and plant material. Despite the wide spectrum of biological activity of propolis, to our knowledge no studies have been carried out about phytotoxic properties of Brazilian propolis and its constituents. The aims of this study were to analyze the chemical composition and to evaluate the phytotoxic activity of the volatile fraction of a sample of Brazilian green propolis. RESULTS: Main constituents are the phenylpropanoid 3-prenylcinnamic acid allyl ester (26.3%) and the sesquiterpene spathulenol (23.4%). Several other sesquiterpenes and phenylpropanoids, in addition to linalool and α-terpineol (monoterpenes), were also detected. The activity of solutions of the volatile fraction at 1.0, 0.5 and 0.1% was tested on lettuce seeds and seedlings. The solution at 1% inhibited completely the seed germination and solutions at 0.1 and 0.5% reduced the germination rate index. The solution at 0.5% reduced the growth of the hypocotyl-radicle axis and the development of the cotyledon leaf. CONCLUSIONS: The chemical composition of the volatile fraction of this Brazilian green propolis is different from those previously described, and these results may contribute to a better understanding about the chemical variations in propolis. The volatile fraction of Brazilian green propolis influences both germination of seed lettuce and the growth of its seedlings, showing an phytotoxic potential.

Does propolis contain tannins?

Although polyphenols have been reported as common constituents of propolis, tannins have rarely been mentioned as its constituents. Propolis samples from seven localities in Brazil were analyzed for detection of proanthocyanidins (condensed tannins) and determination of the tannin content. Positive reaction for proanthocyanidins was observed for all samples tested. The contents of tannins varied in the range 0.6-4.1%. A high degree of correlation was noted between total phenols and tannin content. Red and green propolis contained high contents of tannins, while in brown propolis the content was lower. It is suggested that the contents of tannins should be a parameter to be considered in propolis characterization.

Fermentation medium for collagenase production by Penicillium aurantiogriseum URM4622.

Medium composition and culture conditions for maximal collagenase production by Penicillium aurantiogriseum URM4622 were optimized using a response surface approach. A full two-level design on three factors (initial medium pH, soybean flour concentration, and temperature) was employed to identify the most significant fermentation parameters for collagenase production, and a subsequent central composite design (CCD) was used to find the optimal levels of the two most significant factors (initial medium pH and soybean flour concentration). The design results indicated that the initial medium pH and the temperature had significant negative main effects, whereas the substrate concentration had a positive effect on the collagenase production. The maximum collagenolytic activity predicted by the fitted response surface was expected to occur at pH 7.21, 1.645% soybean flour concentration and 24°C. Three replicate experiments were run at these conditions and yielded an activity response of 283.36 ± 1.33 U, which not only is the highest obtained in this study but also represents a 5-fold increase over the lowest response observed in the initial design. Since all experiments were carried out with an inexpensive substrate, the final results point out to a cost-effective medium for collagenase production with potential industrial-scale applications.