This work describes a green synthesis, the characterization, and biological evaluation of silver nanoparticles (AgNPs). The AgNPs suspension was synthesized using aqueous leaf extract of Eucalyptus grandis, which presented a characteristic band at 407 nm in the UV-Vis spectrum. The AgNPs presented a spherical shape and size of 9.7 ± 0.3 nm. The nanoparticles were stable over a month, indicating that E. grandis’ extract is suitable for their preparation and stabilization. The X-ray analysis showed that the crystallinity of AgNPs corresponded to the centered face phase of silver. The antibacterial and leishmanicidal activities of AgNPs were evaluated. The AgNPs presented antibacterial activity on the Gram-negative bacteria Escherichia coli at 53.9 µg mL-1. The leishmanicidal activity evaluation against promastigote forms of Leishmania infantum, Leishmania amazonensis, and Leishmania braziliensis showed that the biological response is dependent on the volume of AgNP suspension. It was demonstrated that L. infantum was more sensitive to the nanoparticle’s treatment than L. amazonensis and L. braziliensis. The treatment of L infantum promastigotes with 150 µL of AgNP suspension reduced parasite growth by 67.9%, a result which was similar to the treatment with 1 (66.7%) or 2 µL (70.6%) of amphotericin B used as a positive control.

The fungal Hemileia vastatrix is the causal agent of coffee leaf rust, one of the worst and devastating disease in coffee cultures worldwide. As a result of our research on natural products for the development of novel agrochemicals, we found that the hexane extract from leaves of the Brazilian medicinal plant Garcinia gardneriana, at 500 μg mL-1, inhibited in 98% the germination of H. vastatrix urediniospores. This extract showed no phytotoxicity when tested for seed germination and seedling growth inhibitory activity using sensible plant species. Also, the hexane extract from leaves was tested for anti-acetylcholinesterase activity, which constitutes a mechanism of action of major commercial insecticides used in agriculture, and showed low activity even at concentrations about two times higher than the half maximal inhibitory concentration (IC50) found in the antifungal assays. Gas chromatography-mass spectrometry (GC-MS) analysis showed that the hexane extract is constituted mainly by the pentacyclic triterpene lupeol, together with a series of sesquiterpenes as minor components. This is the first report on the investigation of antifungal, phytotoxic and acetylcholinesterase activities of extracts from leaves of G. gardneriana. These findings indicate that G. gardneriana may constitute a promising source of natural products for controlling the coffee leaf rust fungus.

A previous study for the identification of acetylcholinesterase (AChE) inhibitors demonstrated that the hybrid between tyrosol, the 1,2,3-triazole nucleus, and the coumarin group, namely 7-({1-[2-(4-hydroxyphenyl)ethyl]-1H-1,2,3-triazol-4-yl}methoxy)-4-methyl-2H-chromen-2-one (10), has a high enzyme inhibitory activity. Here, we synthesized analogues of 10 via triazole with pharmacophoric groups represented by tyrosine, phenylalanine, tryptophan, and glycine in addition to evaluating the impact of coumarin-linked amino acids on AChE inhibition. We obtained eight triazoles, six of which are undescribed. In general, the presence of carboxylic acid decreased the inhibitory activity, while aromatic amino acids increased enzymatic inhibition compared to glycine. The derivative containing tyrosine, structurally most similar to 10, presented the lowest inhibition percentage, indicating that phenolic hydroxyl is not the preponderant factor for inhibition. Molecular docking was not enough to explain in vitro experiments. On the other hand, MlogP (logP calculated by the Moriguchi method) was related positively to enzymatic inhibition. To increase the hydrophobicity of the molecules, we tested the esterified triazole derivatives comparatively with the enzyme. The compound ethyl 2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate (6) presented an increment of inhibitory activity of 46.97 ± 1.75% at 100 μmol L-1. We also associated the best activity with the lowest van der Waals volume and molar mass values.

Carpotroche brasiliensis is a tree native to Brazil, belonging to the family Flacurtiaceae, whose seeds contain a group of cyclopentenyl fatty acids: gorlic (12%), chaulmugric (27%), and hydnocarpic (48.7%). These compounds are considered the main therapeutic agents in the treatment of leprosy. In the present study, a series of novel triazole compounds were obtained by conjugation between hydnocarpic acid and functionalized azides via copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Hydnocarpic acid and its derivatives were tested against estrogen-positive breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and non-small cell lung cancer (A549) cell lines. The (R)-(1-(pyridin-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl-11-(cyclopent-2-en-1-yl)undecanoate (8) displayed promising antiproliferative activity against A549 cells. We demonstrated that this compound selectively inhibited the viability of A549 cell cultures. Furthermore, compound 8 inhibited the clonogenic capacity of A549 cells, and this effect was associated to its ability to inhibit cell cycle progression at G1 phase. These findings indicate that 8 is a promising antitumor agent on A549 cells and support further studies to evaluate the molecular mechanisms underlying its antiproliferative activity. In addition, hydnocarpic acid should be considered as a promising chemical prototype to obtain novel antineoplastic agents.

The Z-E isomerization of γ-alkylidenebutenolide analogues to natural nostoclides and other natural butenolides was investigated using 1H nuclear magnetic resonance (NMR) and high performance liquid chromatography (HPLC) data as well as density functional theory (DFT) calculations at the wB97x-D/6-31G(d,p) level, including solvent effects with the polarizable continuum solvation approach. The experimental data supported the Z to E isomerization of γ-alkylidenebutenolides under acid catalysis. Newly prepared samples have predominantly Z configuration, which partially isomerizes to the E isomer under acidic conditions. Density functional theory studies corroborate the experimental findings. While neutral γ-alkylidenebutenolides are more stable in the Z form, protonation of the γ-lactone carbonyl group results in preferential stabilization of the E isomer.