Search Results (72)

The year 2024 marked the 80th anniversary of Woodward’s total synthesis of quinine. Quinine is a natural alkaloid from the bark of the cinchona tree that has been used for years as an antimalarial drug. The antibacterial effect of quinine salts has also been regarded. With this in mind, a series of original 9-deoxycinchone alkaloid derivatives bearing a dialkylamino- or heterocyclic moiety at the 4 position of the 9-(((4-X-but-2-ynyloxy)methyl)-1,2,3-triazolyl)-substituent was synthesized. The copper-catalyzed three-component A³-coupling reaction of 9-(((4-prop-2-ynyloxy)methyl)-1,2,3-triazolyl)- substituted cinchona alkaloid derivatives with secondary amines and formaldehyde was the main route of synthesis. The present study attempted to examine the antibacterial properties of 9-substituted 9-desoxyquinine-derived compounds and their antibacterial activity against pathogenic bacterial strains, e.g., Staphylococcus aureus, Bacillus subtillis, Bacillus cereus, and Escherichia coli. The difference in the antibacterial activity profile of diastereoisomeric 9-(((4-X-but-2-ynyloxy)methyl)-1,2,3-triazolyl)-substituted derivatives of cinchona alkaloids indicated the importance of the nature of nitrogen substituents in the molecules. In a concentration-dependent pattern, (9R)- and (9S)- (((4-asocan-1yl)-but-2-ynyl-oxy)methyl)-1,2,3-triazolyl)-substituted compounds demonstrated considerable biofilm-inhibitory efficacy against the S. aureus bacterial strain. A detailed study of the molecular interactions with the targeted protein MurB was performed using docking simulations, and the obtained results are quite promising. Full article

What is a plant? A photosynthesizing organism, molecule, commodity, songs, images, oniric experience, spirit…Indigenous perspectives show that plants cannot be thought of without the relationships that constitute them. We contextualize our reflection in plant extractive activities that, by reducing sociality with these non-humans to anonymous, non-situated knowledge, feed a transit of knowledge based on a relational extractivism. Thus, in this article, based on one historical case and another ethnographic one involving two South American plants—cinchona (Cinchona officinalis) and matico (Piper aduncum)—we present a reflection on plant agency from the perspective of Amazonian peoples, with the intention of showing how these beings are conceived of as subjects who are part of kinship relations, but also of predation. We take shamanic and artistic experiences as ethnographic cases to argue that the Western categories of biology are insufficient to define and circumscribe the so-called plant kingdom according to certain Amazonian conceptions. Full article

A novel and general approach to the practical ROMP polymerization of cinchona alkaloid derivatives providing novel hybrid materials having quinine attached on a poly(norbornene-5,6-dicarboxyimide) matrix is presented. The concept involves an easy modification of quinine (in general, any cinchona alkaloid) toward clickable 9-azide that reacts with N-propargyl-cis-5-norbornene-exo-2,3-dicarboxylic imide in Cu(I)-catalyzed Huisgen cycloaddition (click chemistry). The resulting monomers undergo a controllable ROMP reaction that leads to novel polymers of a desired length and solubility. This sequence allows for the facile preparation of a regularly decorated polymeric material having one quinine moiety per single mer of the polymer chain inaccessible using typical immobilization methods. A poly(norbornene-5,6-dicarboxyimide) type of polymeric matrix was selected due to the high reactivity of the exo-norbornene motif in Ru(II)-catalyzed ROMP and its chemical and thermal stability as well as convenient, scalable access from inexpensive cis-5-norbornene-exo-2,3-dicarboxylic anhydride (‘one-pot’ Diels–Alder reaction of dicyclopentadiene and maleic anhydride). An appropriate combination of a Grubbs catalyst, Ru(II) (G1, G2), and ROMP conditions allowed for the efficient synthesis of well-defined soluble polymers with mass parameters in the range Mn = 2.24 × 10⁴ – 2.26 × 10⁴ g/mol and Mw = 2.90 × 10⁴–3.05 × 10⁴ g/mol with good polydispersity, Đ_M = 1.32–1.35, and excellent thermal stability (up to 309°C T_d10). Spectroscopic studies (NMR and electronic circular dichroism (ECD)) of these products revealed a linear structure with the slight advantage of a trans-configuration of an olefinic double bond. The resulting short-chain polymer discriminates mandelic acid enantiomers with a preference for the (R)-stereoisomer in spectrofluorimetric assays. This concept seems to be rather general with respect to other molecules dedicated to incorporation into the poly(norbornene-5,6-dicarboxyimide) chain. Full article

Novel peptides based on common amino acid building blocks may serve as possible drug candidates; however, their flexible structures may require stabilization via the incorporation of conformational constraints. The insertion of unusual amino acids is a feasible option that may provide improved pharmacokinetic and pharmacodynamic properties of such peptide-type drugs. The stereochemical purity of these kinds of building blocks must be verified by an efficient separation technique, such as high-performance liquid chromatography. Here, we present and discuss the results of the stereoselective separation mechanism of ß-methylated phenylalanine (ß-MePhe), tyrosine (ß-MeTyr), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (ß-MeTic), and cyclohexylalanine (ß-MeCha) together with non-methylated Phe, Tyr, Tic, and Cha applying Cinchona alkaloid-based chiral stationary phases (CSPs). The studied zwitterionic CSPs acting as ion exchangers provided optimal performance in the polar ionic mode when methanol or a mixture of methanol and acetonitrile was utilized as the mobile phase together with organic acid and base additives. It was found that the basicity of small amines applied as mobile phase additives did not directly influence the chromatographic ion exchange concept. However, the size of the amines and their concentration led to a reduced retention time following the principles of ion exchange chromatography. On the basis of a systematic study of the effects of the eluent composition on the chromatographic behavior, important structure–retention and enantioselectivity relationships could be revealed. Through a temperature study, it has become evident that the composition of the eluent and the structure of analytes markedly affect the thermodynamic properties. Full article

An effective deposition of a cinchonine layer on a platinum metal surface can be easily achieved through the cathodic reduction of a cinchonine hydrochloride methanolic solution at a controlled potential of −220 mV vs. the silver standard electrode (SSE). A coated screen-printed platinum electrode has proven to be suitable for cinchonine determination in water, urine, and serum at µg L⁻¹ concentration levels using differential pulse voltammetry in a phosphate buffer solution (pH 7.0). The limits of detection (LOD) and quantitation (LOQ) were 0.6 µg L⁻¹ and 1.8 µg L⁻¹, respectively. Full article

Helopeltis cinchonae is an emerging pest of tea and causes severe damage to tea plantations in China. The female of H. cinchonae has been reported to produce a sex pheromone consisting of two components, hexyl (3R)-3-acetoxybutyrate and (5R)-1-acetoxy-5-butyroxyhexane, and lures containing the synthetic compounds have been shown to attract male H. cinchonae to traps in the field. This is the first time that components of the sex pheromone have been identified for a species of Helopeltis bug, but their field application has not been evaluated in detail. The present study shows that a blend of both compounds loaded into a polyethylene vial at 0.2 and 2 mg, respectively, caught significantly more male H. cinchonae bugs than the individual compounds and all the other tested blends. Sticky wing traps baited with the binary blend of compounds at the optimized ratio and dosage caught more bugs than bucket funnel or delta traps, and traps hung at a height of 10 cm above the tea shoots caught more bugs than those at other heights. The optimized traps and lures were used for monitoring the pest and two distinct population peaks of H. cinchonae were observed, the first one during mid-May to early June, and the other one in mid-September. Overall, the results of this study contribute to an environmentally-friendly approach to monitoring and managing H. cinchonae in the field. Full article

This study successfully optimized two advanced extraction methods, microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), for the efficient and rapid recovery of quinine from Cinchona officinalis. Among the evaluated parts of the plant, the bark consistently yielded the highest quinine concentration, highlighting its significance as the primary source for alkaloid extraction. The optimized conditions for MAE (65% ethanol, 130 °C, 34 min) achieved a maximum yield of 3.93 ± 0.11 mg/g, while UAE (61% ethanol, 25 °C, 15 min) provided a faster but slightly lower yield of 2.81 ± 0.04 mg/g. These findings confirm the superiority of MAE and UAE over conventional methods like Soxhlet extraction in terms of time efficiency and sustainability. The quantification of quinine using high-performance liquid chromatography (HPLC) coupled with advanced detection methods further validated the reliability and reproducibility of the results. While this study focused on optimizing extraction and quantification parameters, it sets the groundwork for future research into the sustainable utilization and potential valorization of C. officinalis byproducts. These findings not only provide a standardized protocol for extracting quinine but also contribute to the broader application of green chemistry principles in pharmaceutical production. Full article

This study evaluated the germination of Cinchona spp. seeds under controlled environmental conditions within a geodesic dome equipped with photovoltaic energy. The main objective was to assess how stable temperature and humidity, along with potassium nitrate (KNO₃) and specific LED light treatments, affect the germination rate and plant growth. The results indicate that Cinchona spp. seeds germinate effectively inside the dome, even under temperature and humidity conditions that differ from their natural habitat. Among the evaluated conditions, the treatment with 1000 ppm of KNO₃ and white LED light (LM 1000 ppm) showed the highest germination rate, achieving 72.5% with an average of 1.5 seeds germinated per day. Agronomic evaluations showed that this treatment also led to superior growth metrics, including an average plant height of 2.1 cm, an average leaf count of 3.6, and a dry weight of 0.0013 g. This research highlights the potential of controlled environments, such as geodesic domes, to optimize germination and early growth in endangered plant species. The combination of environmental control with KNO₃ treatments offers a valuable approach to enhancing the propagation of Cinchona spp., providing practical implications for conservation and reforestation efforts. This work provides a foundation for further studies on optimizing germination and growth conditions for other native and endangered species in controlled environments. Full article

The use of chiral organic ligands as linkers and metal ion nodes with specific coordination geometry is an effective strategy for creating homochiral structures with potential ferroelectric properties. Natural Cinchona alkaloids, e.g., quinine and cinchonine, as compounds with a polar quinuclidine fragment and aromatic quinoline ring, are suitable candidates for the construction of molecular ferroelectrics. In this work, the compounds [CnZnCl₃]·MeOH and [CnZnBr₃]·MeOH, which crystallize in the ferroelectric polar space group P2₁, were prepared by reacting the cinchoninium cation (Cn) with zinc(II) chloride or zinc(II) bromide. The structure of [CnZnBr₃]·MeOH was determined from single-crystal X-ray diffraction analysis and was isostructural with the previously reported chloride analog [CnZnCl₃]·MeOH. The compounds were characterized by infrared spectroscopy, and their thermal stability was determined by thermogravimetric analysis and temperature-modulated powder X-ray diffraction experiments. The intermolecular interactions of the different cinchoninium halogenometalate complexes were evaluated and compared. Full article

In the field of nutritional science and metabolic disorders, there is a growing interest in natural bitter compounds capable of interacting with bitter taste receptors (TAS2Rs) useful for obesity management and satiety control. This study aimed to evaluate the effect of a nutraceutical formulation containing a combination of molecules appropriately designed to simultaneously target and stimulate these receptors. Specifically, the effect on CCK release exerted by a multi-component nutraceutical formulation (Cinchona bark, Chicory, and Gentian roots in a 1:1:1 ratio, named Gengricin^®) was investigated in a CaCo-2 cell line, in comparison with Cinchona alone. In addition, these nutraceutical formulations were tested through a 3-month randomized controlled trial (RCT) conducted in subjects who were overweight–obese following a hypocaloric diet. Interestingly, the Gengricin^® group exhibited a significant greater weight loss and improvement in body composition than the Placebo and Cinchona groups, indicating its effectiveness in promoting weight regulation. Additionally, the Gengricin^® group reported higher satiety levels and a significant increase in serum CCK levels, suggesting a physiological basis for the observed effects on appetite control. Overall, these findings highlight the potential of natural nutraceutical strategies based on the combination of bitter compounds in modulating gut hormone release for effective appetite control and weight management. Full article

The genus Cinchona L. has important medicinal, cultural, and economic value and is the emblematic tree of Peru. The genus is mainly found in the cloud forests of the Andes. However, the expansion of agriculture and livestock farming in the department of Amazonas is degrading these ecosystems and has reduced the size of the genus’s populations. In this work, we model the potential distribution under current conditions of three Cinchona species (C. capuli L. Anderson, C. macrocalyx Pav. Ex DC., and C. pubescens Vahl.) to identify areas with a high likelihood of species presence and their key conservation and reforestation zones. We fitted a maximum entropy (MaxEnt) model using nineteen bioclimatic variables, three topographic variables, nine edaphic variables, and solar radiation. Under current conditions, the potential distribution of C. capuli covers 17.22% (7243.98 km²); C. macrocalyx, 29.11% (12,238.91 km²); and C. pubescens, 22.94% (9647.63 km²) of the study area, which was mostly located in central and southern Amazonas. Only 24.29% (25.51% of C. capuli, 21.02% of C. macrocalyx, and 26.35% of C. pubescens) of the potential distributions are within protected areas, while 10,987.22 km² of the surface area of the department of Amazonas is degraded, of which 29.80% covers the area of probable occurrence of C. capuli, 38.72% of C. macrocalyx, and 34.82% of C. pubescens. Consequently, it is necessary to promote additional conservation strategies for Cinchona, including the establishment of new protected areas and the recovery of degraded habitats, in order to protect this species. Full article

A series of novel triazole-tethered ferrocenoylamino-substituted cinchona–chalcone hybrids along with two representative benzoylamino-substituted reference compounds were prepared by three methods of CuAAC chemistry. In line with the limited success or complete failure of attempted conversions with low catalyst loadings, by means of DFT modeling studies, we demonstrated that a substantial part of the Cu(I) ions can be chelated and thus trapped in the aroylamino-substituted cinchona fragment and all of the accessible coordinating sites of the chalcone residues. Accordingly, increased amounts of catalysts were used to achieve acceptable yields; however, the cycloadditions with para-azidochalcones were accompanied by partial or complete aldehyde-forming hydrolytic fission of the enone C=C bond in a substituent-, solvent- and copper load-dependent manner. The experienced hydrolytic stability of the hybrids obtained by cycloadditions with ortho-azidochalcones was interpreted in terms of relative energetics, DFT reactivity indices and MO analysis of simplified models of two isomer copper–enone complexes. The novel hybrids were evaluated on HeLa, MDA-MB-231 and A2780 cell lines and showed substantial activity at low-to-submicromolar concentrations. An organometallic model carrying 3,4,5-trimethoxyphenyl residue in the enone part with a para-disubstituted benzene ring in the central skeletal region was identified as the most potent antiproliferative lead, characterized by submicromolar IC₅₀ values measured on the three investigated cells. The biological assays also disclosed that this ferrocenoylamino-containing lead compound displays a ca. two- to five-fold more substantial antiproliferative effect than its benzoylamino-substituted counterpart. Full article

Obesity is a risk factor for several diseases present worldwide. Currently, dietary changes and physical activity are considered the most effective treatment to reduce obesity and its associated comorbidities. To promote weight loss, hypocaloric diets can be supported by nutraceuticals. The aim of this study was to evaluate the effects of a hypocaloric diet associated with Cinchona succirubra supplementation on satiety, body weight and body composition in obese subjects. Fifty-nine overweight/obese adults, were recruited, randomized into two groups and treated for 2 months. The first group (32 adults) was treated with a hypocaloric diet plus cinchona supplementation (the T-group); the second one (27 adults) was treated with a hypocaloric diet plus a placebo supplementation (the P-group). Anthropometric-measurements as well as bioimpedance analysis, a Zung test and biochemical parameters were evaluated at baseline and after 60 days. T-group adults showed significant improvement in nutritional status and body composition compared to those at the baseline and in the P-group. Moreover, T-group adults did not show a reduction in Cholecystokinin serum levels compared to those of P-group adults. In conclusion, our data demonstrate that a hypocaloric diet associated with cinchona supplementation is effective in inducing more significant weight loss and the re-establishment of metabolic parameters than those obtained with a hypocaloric diet. Full article

A simple and rapid access to fluorinated dithioesters was developed by a one-pot sequence corresponding to a Grignard reaction—Mitsunobu type substitution. These activated dithioesters have shown excellent reactivity in an aminolysis reaction from simple or more complex primary amines such as cinchona alkaloids. A stoichiometric amount of amine was sufficient to prepare various thioamides, including a 4-styrenylthioamide cinchonidine monomer, under environmentally friendly conditions, at room temperature, and in a very short time. Full article