Cryptocarya alba is an important tree species in the Chilean sclerophyllous forest. Its leaves and bark are used in traditional medicine to treat liver diseases and rheumatism. Analyses of the essential oil (EO) show serious discrepancies, and information on other constituents is limited. The aerial biomass of individual trees from 3 wild populations, some old trees, and farmed saplings were analyzed (n = 132). The EO profiles were studied by gas chromatography/mass spectrometry (GC/MS). The alkaloidal and polyphenol compositions were determined by ultra-high-performance liquid chromatography (UHPLC)/MS-MS. The total polyphenol content, the total flavonoid content, and the antioxidant capacity (diphenylpicrylhydrazyl, azinobisethylbenzothiazolinesulfonic acid, and ferric reducing antioxidant power: DPPH, ABTS, and FRAP respectively) were determined by standard methods. Significant differences were found at the individual and population levels in the contents of polyphenols, total flavonoids, antioxidant capacity, and specific alkaloids for leaves, bark, and wood. Farmed saplings grown under less light showed higher concentrations of higenamine, N-methylcoclaurine, N-methyllaurotetanine, and isocorydine, while those receiving more light were richer in laurolitsine, boldine, coclaurine, catechin, quercetin, epicatechin, quercitrin, and procyanidins. Important variations were found according to the season, age of the tree and of the leaves. The EO composition also varied considerably. These results support the idea that the natural variability of medicinal species is an important subject for study.

Telomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus, is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N-benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase. The crystal structure of TERT, the catalytic subunit of telomerase from Tribolium castaneum, was used for docking and molecular dynamics analysis. The qTRAP-ligand data gave an IC₅₀ value of about 0.17 ± 0.1 µM for BSB, roughly 400 times stronger than boldine, while the LD₅₀ in the cytotoxicity assays were 12.5 and 21.88 µM, respectively, in cells treated for 48 h. Although both compounds interacted well with the active site, MD analysis suggests a second binding site with which BSB interacts via two hydrogen bonds, much more strongly than boldine. Theoretical analyses also evaluated the IC₅₀ for BSB as submicromolar. BSB, with greater hydrophobicity and flexibility than boldine, represents a promising structure to inhibit telomerase at non-toxic concentrations.

This study presents the potential role of deep eutectic solvents (DESs) in a lipase-catalyzed hydrolysis reaction as a co-solvent in an aqueous solution given by a phosphate buffer. Ammonium salts, such as choline chloride, were paired with hydrogen bond donors, such as urea, 1,2,3-propanetriol, and 1,2 propanediol. The hydrolysis of p-nitrophenyl laureate was carried out with the lipase Candida antarctica Lipase B (CALB) as a reaction model to evaluate the solvent effect and tested in different DES/buffer phosphate mixtures at different $\% w/w$. The results showed that two mixtures of different DES at 25 $\% w/w$ were the most promising solvents, as this percentage enhanced the activities of CALB, as evidenced by its higher catalytic efficiency ($\frac{k_{cat}}{K_M}$). The solvent analysis shows that the enzymatic reaction requires a reaction media rich in water molecules to enable hydrogen-bond formation from the reaction media toward the enzymatic reaction, suggesting a better interaction between the substrate and the enzyme-active site. This interaction could be attributed to high degrees of freedom influencing the enzyme conformation given by the reaction media, suggesting that CALB acquires a more restrictive structure in the presence of DES or the stabilized network given by the hydrogen bond from water molecules in the mixture improves the enzymatic activity, conferring conformational stability by solvent effects. This study offers a promising approach for applications and further perspectives on genuinely green industrial solvents.

Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC—such as 5-fluorouracil (5FU)—remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP⁺C₁₀), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP⁺C₁₀), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP⁺C₁₀ with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP⁺C₁₀ and TPP⁺C₁₀ using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP⁺C10 and TPP⁺C₁₀, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP⁺C₁₀ and GA-TPP⁺C₁₀ increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.