Physicochemical Investigation of Psoralen Binding to Double Stranded DNA through Electroanalytical and Cheminformatic Approaches.

This work showcased the first physicochemical investigation of psoralen (PSO) binding to double stranded DNA (dsDNA) through electroanalytical methods. Results evidenced that PSO presents one non-reversible anodic peak at electric potential (Epa) ≈ 1.42 V, which is associated with its oxidation and the formation of an epoxide derivative. Moreover, PSO analytical signal (i.e., faradaic current) decreases linearly with the addition of dsDNA, while the electric potential associated to PSO oxidation shifts towards more positive values, indicating thence that dsDNA addition hinders PSO oxidation. These findings were corroborated by the chemoinformatic study, which evidenced that PSO intercalated noncovalently at first between base-pairs of the DNA duplex, and then irreversibly formed adducts with both DNA strands, leading up to the formation of a cross-link which bridges the DNA helix, which explains the linear dependence between the faradaic current generated by PSO oxidation and the concentration of DNA in the test-solution, as well as the dependence between Ep and the addition of dsDNA solution. Therefore, the findings herein reported evidence of the applicability of electroanalytical approaches, such as voltammetry in the study of DNA intercalating agents.

Phytochemical Analysis and Antimicrobial Activity of Myrcia tomentosa (Aubl.) DC. Leaves.

This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and purify the extract of the M. tomentosa leaves and the chemical structures of the compounds were determined using spectroscopic techniques. The antibacterial and antifungal activities were assessed using the broth microdilution method. The phytochemical investigation isolated 11 compounds: α-bisabolol, α-bisabolol oxide B, α-cadinol, ß-sitosterol, n-pentacosane, n-tetracosane, quercetin, kaempferol, avicularin, juglanin and guaijaverin. The crude ethanolic extract and its fractions were tested against 15 bacteria and 9 yeasts. The crude extract inhibited the in vitro growth of yeasts at concentration of 4 to 32 µg/mL. The hexane, dichloromethane, ethyl acetate and aqueous fractions inhibited Candida sp. at concentrations of 4 to 256 µg/mL, whereas the Cryptococcus sp. isolates were inhibited only by the hexane and dichloromethane fractions in minimal inhibitory concentrations (MICs) at 16 to 64 µg/mL. The flavonoid quercetin-3-O-α-arabinofuranose (avicularin) was the most active compound, inhibiting Candida species in concentrations of 2 to 32 µg/mL. The MIC values suggest potential activity of this plant species against yeast.

Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part I: Aspidosperma nitidum (Benth) used as a remedy to treat fever and malaria in the Amazon.

Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region. Several species of this family are known to possess indole alkaloids and other classes of secondary metabolites, whereas terpenoids, an inositol and the indole alkaloids harmane-3 acid and braznitidumine have been described in A. nitidum . In the present study, extracts from the wood bark, leaves and branches of this species were prepared for assays against malaria parasites and cytotoxicity testing using human hepatoma and normal monkey kidney cells. The wood bark extracts were active against Plasmodium falciparum and showed a low cytotoxicity in vitro, whereas the leaf and branch extracts and the pure alkaloid braznitidumine were inactive. A crude methanol extract was subjected to acid-base fractionation aimed at obtaining alkaloid-rich fractions, which were active at low concentrations against P. falciparum and in mice infected with and sensitive Plasmodium berghei parasites. Our data validate the antimalarial usefulness of A. nitidum wood bark, a remedy that can most likely help to control malaria. However, the molecules responsible for this antimalarial activity have not yet been identified. Considering their high selectivity index, the alkaloid-rich fractions from the plant bark might be useful in the development of new antimalarials.

Piper peltatum: biomass and 4-nerolidylcatechol production.

Piper peltatum L. is used for the treatment of inflammation, malaria, and other ailments. 4-Nerolidylcatechol (4-NC) is a valuable natural product that has important anti-inflammatory, antimalarial, and antioxidant properties. 4-NC is a component of P. peltatum and P. umbellatum extracts, which are used in cosmetics. The aim of this work was to evaluate the production of plant biomass and the production of 4-NC in roots of cultivated P. peltatum over a full life cycle. Seedlings were produced in a greenhouse and then transplanted. The weight of dry plant parts (leaves, stems, roots, and inflorescences); numbers of stems, leaves, and inflorescences; and the leaf-to-stem ratio were evaluated at intervals of 60 days after transplanting (DAT). Extracts were prepared using 1:1 ethanol-chloroform and an ultrasound bath. Roots, leaves, and inflorescences contained 4-NC according to TLC photodensitometry analysis. Quantification of 4-NC in root extracts was performed using HPLC-DAD analysis. Per-hectare production of 4-NC by roots was estimated based on quantitative HPLC analysis and biomass data. Optimal per-hectare yields of 4-NC were obtained by harvesting roots between 350 and 400 DAT. In this period, the average yield was 27 kg 4-NC per hectare. Importantly, at the time of maximal overall production of root biomass (470 DAT), there was a decrease in the production of 4-NC (23.8 kg/ha), probably due to the onset of senescence.

Production of an antiproliferative furanoheliangolide by Lychnophora ericoides cell culture.

This work reports for the first time the production a furanoheliangolide (goyazensolide) by plant cell culture. Monitoring of the goyazensolide metabolism revealed that the maximum production occurred during the lag phase of the Lychnophora ericoides callus culture. The antiproliferative activity of obtained goyazensolide was evaluated against seven cancer cell lines using MTT assay. The results revealed a potent cytotoxic activity for the furaheliangolide with IC50 values in the range of 0.06 microg/ml for CEM leukemia cells to 0.75 microg/ml for B16 melanome cells.