Novel anticancer PdII complexes: The effect of the conjugation of transferrin binding peptide and the nature of halogen coordinated on antitumor activity.

A series of PdII complexes with bis-(2-pyridylmethyl)glycine as a ligand of formula [PdX(bis-(2-pyridylmethyl)glycine)] where X = Cl, Br, I were prepared and the effect of the halogen nature in the antitumor activity of eight tumorigenic and one non-tumorigenic cell line was evaluated. The chloride derivative was further functionalized with a transferrin receptor binding peptide, generating the first PdII based metallopeptide. Its antitumor activity was also evaluated. However, among all the complexes, the chloride and iodine parent compounds showed the lowest GI50 values in the panel evaluated, and lowest GI50 than cisplatin in several cell lines. In contrast, the bromine derivative showed higher values of GI50 than chloride and iodine (around 30 - 50 µM). The same trend was observed for the bovine serum albumin binding constant with higher values for iodine, chlorine, and bromine in this order. In aqueous solution, the chloride is exchanged by water while the bromine and iodine are not. DNA was evaluated as a target and showed no significative interaction for all the compounds. The results suggest sulfur-rich proteins and not DNA as a target. This report represents the first PdII metallopeptide reported, its evaluation in solution and antitumor activity. This work opens the possibilities for further functionalization of PdII complexes and the importance of the halogen coordination in the design of novel metallodrugs.

Linear gold(I) complex with tris-(2-carboxyethyl)phosphine (TCEP): Selective antitumor activity and inertness toward sulfur proteins.

The search for modulating ligand substitution reaction in gold complexes is essential to find new active metallo compounds for medical applications. In this work, a new linear and hydrosoluble goldI complex with tris-(2-carboxyethylphosphine) (AuTCEP). The two phosphines coordinate linearly to the metal as solved by single crystal X-ray diffraction. Complete spectroscopic characterization is also reported. In vitro growth inhibition (GI50) in a panel of nine tumorigenic and one non-tumorigenic cell lines demonstrated the complex is highly selective to ovarium adenocarcinoma (OVCAR-03) with GI50 of 3.04 nmol mL-1. Moreover, non-differential uptake of AuTCEP was observed between OVCAR-03 (tumor) and HaCaT (non-tumor) two cell lines. Biophysical evaluation with the sulfur-rich biomolecules showed the compound does not interact with two types of zinc fingers, bovine serum albumin, N-acetyl-l-cysteine and also l-histidine, revealing to be inert to ligand substitution reactions with these molecules. However, AuTCEP demonstrated to cleave plasmidial DNA, suggesting DNA as a possible target. No antibacterial activity was observed in the strains evaluated. Besides, it inhibits 15% of the activity of a mixture of serine-ß-lactamase and metallo-ß-lactamase from Bacillus cereus in the enzymatic activity assay, similarly to EDTA. These results suggest AuTCEP is selective to metallo-ß-lactamase but the cell uptake is hindered, and the compound does not reach the periplasmic space of Gram-positive bacteria. The unique inert behavior of AuTCEP is interesting and represent the modulation of the reactivity through coordination chemistry to decrease the toxicity associated with AuI complexes and its lack of specificity, generating very selective compounds with unexpected targets.

Bioactive compounds and antioxidant capacity of buriti (Mauritia flexuosa L.f.) from the Cerrado and Amazon biomes.

Pulp of buriti palms (Mauritia flexuosa L.f.) from two Brazilian regions had their phenolic and carotenoid contents and antioxidant capacity evaluated through different methods (ABTS, DPPH, FRAP and ORAC). Buriti pulp from the Cerrado presented higher phenolic levels (435.08 mg AGE 100 g(-1)) and elevated antioxidant capacity in all tests. The fruits from the Amazon region had a higher total carotenoid content (52.86 mg 100 g(-1)). Carotenoid profile has confirmed ß-carotene predominance in both regions studied. The buritis' region of origin influenced bioactive compound contents and antioxidant capacity of the fruits analyzed. A significant positive correlation (r ⩽ 0.95; p<0.05) was observed between total phenolics and antioxidant capacity through the different methods applied. Results showed promising prospects for the future exploitation of buriti fruits as a potential source of carotenoids and natural antioxidants.

Effects of short-term very low-carbohydrate or conventional diet on strength performance.

AIM: Weight reduction strategies usually include diet and regular physical activity. A very low-carbohydrate and high protein diet (VLCD) may be preferred instead of a low energy conventional diet (CONV). The effects of VLCD on strength performance are yet to be understood. Aim of the study is to determine the effects of two different restrictive diets on strength performance. METHODS: Sedentary women were assigned to either a VLCD (<40 g carbohydrate; n=12) or a CONV diet (500 to 800 kcal restrictive; 48%, 22% and 30% from carbohydrate, protein and fat, respectively; n=12). Knee extension isokinetic strength tests (3 yen 15 reps at 60 degrees .s-1, with 90 or 180 s rest interval between sets) were performed prior and after a one week diet period. RESULTS: Both groups reduced body mass (VLCD: -2.6+/-1.0% vs. CONV: -1.9+/-1.3%; P<0.05), with no between diets effect. The sum of the total work in three sets (ATW) was 4850+/-1002 J vs. 4801+/-973 J with 90 s rest interval, and 4812+/-1174 J vs. 4812+/-1210 J with 180 s rest interval, respectively, in the pre vs. post-VLCD period. For CONV, values were 4709+/-729 J vs. 4530+/-996 J with 90 s rest interval, and 4760+/-732 J vs. 4816+/-702 J with 180 s rest interval, respectively, in the pre vs. post-CONV treatment. No significant differences were detected in the ATW between groups. CONCLUSION: Short-term hypoenergetic diets, irrespective of the carbohydrate content, seem to reduce significantly body mass, but do not impair acute strength performance.