Antibacterial, Trichomonacidal, and Cytotoxic Activities of Pleopeltis crassinervata Extracts.

Pleopeltis crassinervata is a fern documented in ethnobotanical records for its use in Mexican traditional medicine to treat gastric disorders and mouth ulcers. Consequently, conducting biological and pharmacological assays is crucial to validate the therapeutic efficacy of this plant within the context of traditional medicine. In the present study, we investigated the biological activity of extracts and fractions obtained from P. crassinervata organs against bacteria (Salmonella typhimurium, Salmonella typhi, Staphylococcus aureus, Proteus mirabilis, Shigella flexneri, Bacillus subtilis, Escherichia coli) and Trichomonas vaginalis using in vitro models. The precipitate fraction obtained from the frond methanolic extract showed significant antibacterial activity (minimal inhibitory concentration [MIC] 120 µg/mL) against the Staphylococcus aureus strain and was effective against both Gram-positive and Gram-negative bacteria. The hexane fraction also obtained from frond methanolic extract, showed a trichomonacidal effect with an IC50 of 82.8 µg/mL and a low cytotoxic effect. Hsf6 exhibited the highest activity against T. vaginalis, and the GC-MS analysis revealed that the predominant compound was 16-pregnenolone. The remaining identified compounds were primarily terpene-type compounds.

Click synthesis of dendronized malonates for the preparation of amphiphilic dendro[60]fullerenes.

Fullerene C60 and its malonate derivatives, produced via the Bingel-Hirsch reaction, have displayed promising properties against various diseases. These molecules have great therapeutic potential, but their broad use has been limited due to poor aqueous solubility and toxicity caused by accumulation. In this study, we synthesized new malonates and malonamides attached to first- and second-generation polyester dendrons using click chemistry (CuAAC). These dendrons were then linked at C60 through the Bingel-Hirsch reaction, resulting in an amphiphilic system that retains the hydrophobic nature of C60. The dendronized malonate derivatives showed good reaction yields for the Bingel-Hirsch mono-adducts and were easier to work with than the corresponding malonamides. However, the malonamide derivatives, which were obtained through a multistep reaction sequence, showed moderate yields in the Bingel-Hirsch reaction. Surprisingly, removing acetonide protecting groups from dendritic architectures was more challenging than anticipated, likely due to product decomposition. Only the corresponding free malonate derivatives 25 and 26 were obtained, but in a low yield due to decomposition under the reaction conditions. Meanwhile, it was not possible to obtain the corresponding malonamide derivatives 27 and 28. Currently, efforts are being made to improve the production of the desired molecules and to design new synthesis routes that allow direct access to the desired poly-hydroxylated derivatives. These derivatives will be evaluated as multitarget ligands against Alzheimer's disease, through their use as inhibitors of amyloid ß-peptide aggregation, acetylcholinesterase modulators, and antioxidants.

Evaluation of the Anti-Toxoplasma gondii Efficacy, Cytotoxicity, and GC/MS Profile of Pleopeltis crassinervata Active Subfractions.

Pleopeltis crassinervata (Pc) is a fern that, according to ethnobotanical records, is used in Mexican traditional medicine to treat gastrointestinal ailments. Recent reports indicate that the hexane fraction (Hf) obtained from Pc methanolic frond extract affects Toxoplasma gondii tachyzoite viability in vitro; therefore, in the present study, the activity of different Pc hexane subfractions (Hsf) obtained by chromatographic methods was evaluated in the same biological model. Gas chromatography/mass spectrometry (GC/MS) analysis was carried out for hexane subfraction number one (Hsf1), as it showed the highest anti-Toxoplasma activity with a half-maximal inhibitory concentration (IC50) of 23.6 µg/mL, a 50% cytotoxic concentration (CC50) of 398.7 µg/mL in Vero cells, and a selective index (SI) of 16.89. Eighteen compounds were identified by Hsf1 GC/MS analysis, with the majority being fatty acids and terpenes. Hexadecanoic acid, methyl ester was the most commonly found compound (18.05%) followed by olean-13(18)-ene, 2,2,4a,8a,9,12b,14a-octamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,12,12a,12b,13,14,14a,14b-eicosahydropicene, and 8-octadecenoid acid, methyl ester, which were detected at 16.19%, 12.53%, and 12.99%, respectively. Based on the mechanisms of action reported for these molecules, Hsf1 could exert its anti-Toxoplasma activity mainly on T. gondii lipidomes and membranes.

Multiadducts of C60 Modulate Amyloid-ß Fibrillation with Dual Acetylcholinesterase Inhibition and Antioxidant Properties: In Vitro and In Silico Studies.

BACKGROUND: Amyloid-ß (Aß) fibrils induce cognitive impairment and neuronal loss, leading to onset of Alzheimer's disease (AD). The inhibition of Aß aggregation has been proposed as a therapeutic strategy for AD. Pristine C60 has shown the capacity to interact with the Aß peptide and interfere with fibril formation but induces significant toxic effects in vitro and in vivo. OBJECTIVE: To evaluate the potential of a series of C60 multiadducts to inhibit the Aß fibrillization. METHODS: A series of C60 multiadducts with four to six diethyl malonyl and their corresponding disodium-malonyl substituents were synthesized as individual isomers. Their potential on Aß fibrillization inhibition was evaluated in vitro, in cellulo, and silico. Antioxidant activity, acetylcholinesterase inhibition capacity, and toxicity were assessed in vitro. RESULTS: The multiadducts modulate Aß fibrils formation without inducing cell toxicity, and that the number and polarity of the substituents play a significant role in the adducts efficacy to modulate Aß aggregation. The molecular mechanism of fullerene-Aß interaction and modulation was identified. Furthermore, the fullerene derivatives exhibited antioxidant capacity and reduction of acetylcholinesterase activity. CONCLUSION: Multiadducts of C60 are novel multi-target-directed ligand molecules that could hold considerable promise as the starting point for the development of AD therapies.

Acetylcholinesterase inhibition and antioxidant activity properties of Petiveria alliacea L.

ETHNOPHARMACOLOGICAL RELEVANCE: Petiveria alliacea L. is traditionally used as a folk medical herb in different regions of the world to treat different ailments including those related to the central nervous system. Previous studies have proved that extracts from P. alliacea show improvement in memory and learning process. AIM OF THE STUDY: To study extracts, fractions, subfractions and isolated compounds from P. alliacea on acetylcholinesterase inhibition and antioxidant activity. MATERIAL AND METHODS: Extracts obtained with different polarity solvents and fractions from P. alliacea were evaluated for their inhibitory activity on acetylcholinesterase by Ellman method. This screening allowed the selection of the methanol fraction as the most active and continued a bio-guided study. The compounds identified in methanol fraction were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS). Identification of (E)-Tagetone was performed by 1H and 13C NMR spectra. Moreover, the antioxidant activity was evaluated by DPPH and ABTS methods, and the cell viability was assessed by WST-1 method. RESULTS: Two extracts of different polarity were obtained from P. alliacea. The methanol extract and its fraction showed an inhibitory activity on acetylcholinesterase; however, methanol fraction was found to be most potent with 86.5 % AChE inhibition. The methanol fraction also showed antioxidant activity and was not toxic on SH-SY5Y cells. Different compounds including capreoside, narcissin, indane, (-)-isocaryophyllene, (-)-ß-pinene, (E)-tagetone and peonidin 3-O-sambubioside 5-O-glucoside were identified. CONCLUSION: This is the first report indicating that P. alliacea methanol fraction and its subfractions bear acetylcholinesterase inhibition and antioxidant activity properties. This work establishes the basis for further studies in the development of new therapies for neurodegenerative disorders such as Alzheimer 's disease.

Low frequency vortex magnetic field reduces amyloid ß aggregation, increase cell viability and protect from amyloid ß toxicity.

Plaques formed by abnormal accumulation of amyloid ß-peptide (Aß) lead to onset of Alzheimer's disease (AD). Pharmacological treatments do not reduce Aß aggregation neither restore learning and memory. Noninvasive techniques have emerged as an alternative to treat AD, such as stimulation with electromagnetic fields (EMF) that decrease Aß deposition and reverses cognitive impairment in AD mice, even though some studies showed side effects on parallel magnetic fields stimulation. As a new approach of magnetic field (MF) stimulation, vortex magnetic fields (VMF) have been tested inducing a random movement of charged biomolecules in cells, promoting cell viability and apparently safer than parallel magnetic fields. In this study we demonstrate the effect of VMF on Aß aggregation. The experimental strategy includes, i) design and construction of a coil capable to induce VMF, ii) evaluation of VMF stimulation on Aß peptide induced-fibrils-formation, iii) evaluation of VMF stimulation on SH-SY5Y neuroblastoma cell line in the presence of Aß peptide. We demonstrated for the first time that Aß aggregation exposed to VMF during 24 h decreased ~ 86% of Aß fibril formation compared to control. Likewise, VMF stimulation reduced Aß fibrils-cytotoxicity and increase SH-SY5Y cell viability. These data establish the basis for future investigation that involve VMF as inhibitor of Aß-pathology and indicate the therapeutic potential of VMF for AD treatment.

Anti-toxoplasma, antioxidant and cytotoxic activities of Pleopeltis crassinervata (Fée) T. Moore hexane fraction.

The apicomplexan parasite Toxoplasma gondii (T. gondii) causes toxoplasmosis in humans. Pyrimethamine and sulfadiazine that are the drugs of choice to treat the disease, produce severe side effects as well as failure treatments because of drug resistance; thus, novel anti-Toxoplasma compounds are needed and natural compounds can be a good source to obtain them, as medicinal plants have been used to control other apicomplexan parasites. Pleopeltis crassinervata (P. crassinervata) is a fern used in some rural areas of Mexico to treat among other malaises, mouth ulcers, gastrointestinal problems and parasites. Therefore, the efficacy of extracts and fractions obtained from P. crassinervata fronds was evaluated on the viability of T. gondii RH strain tachyzoites by the Stytox green method. RH is the prototypical type 1 Toxoplasma strain, isolated for the first time from the brain of a patient boy named R. H. Its phytochemical profile, MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Hep-2 cytotoxicity and antioxidant activity by ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) methods, were also assessed. Hexane fraction exhibited the highest anti-Toxoplasma activity with an IC50 of 16.90 µg/mL. This fraction did not show antioxidant activity and contained at least 2 terpenoid type compounds with retention factor (Rf) of 0.75 and 0.86. The fraction was not toxic to the host cells in doses up to 50 µg/mL. P. crassinervata frond hexane fraction seems to be a good candidate to obtain possible anti-Toxoplasma compounds. This study is the first to report the biological, antioxidant and cytotoxic activity of P. crassinervata fern.

Histopathological alterations in mice under sub-acute treatment with Hintonia latiflora methanolic stem bark extract.

The indiscriminate use of herbal products is increasingly growing worldwide; nonetheless consumers are not warned about the potential health risks that these products may cause. Hintonia latiflora (Hl) is a tree native to the American continent belonging to the Rubiaceae family and its stem bark is empirically used mainly to treat diabetes and malaria; supplements containing Hl are sold in America and Europe without medical prescription, thus scientific information regarding its toxicity as a consequence of a regular consumption is needed. In the present study, the histopathological effect of 200 and 1000 mg/kg of HI methanolic stem bark extract (HlMeOHe) was evaluated in the small bowel, liver, pancreas, kidneys and brain of CD-1 male mice after oral sub-acute treatment for 28 days. No histopathological alterations were observed in the brain and small bowel of the treated animals; however, mice presented diarrhea from day 2 of treatment with both doses. No histological changes were observed in the tissues collected from the animals treated with 200 mg/kg, except for the liver that depicted periportal hepatitis. Animals treated with the higher dose showed in the liver sections hydropic degeneration, hepatitis and necrosis, kidney sections depicted tubular necrosis and in pancreas sections, hydropic degeneration of the pancreatic islets was observed. In conclusion, HlMeOHe damaged the liver with an oral dose of 200 mg/kg, and at 1000 mg/kg injured the kidneys and pancreas of the CD-1 male mice.

Influence of Eu(3+) doping content on antioxidant properties of Lu2O3 sol-gel derived nanoparticles.

This paper presents the synthesis of pure and europium-doped lutetium oxide (Lu2O3) powders prepared by sol-gel method. The influence of europium ion concentration into Lu2O3 nanocrystallites was investigated for first time in an in vitro system using a modified ABTS radical cation decolorization assay to determine the antioxidant activity. The crystalline structure of Lu2O3 and Eu:Lu2O3 powders was elucidated by XRD obtaining cubic phase in all system without secondary products in accordance with FT-IR results. By TEM and Scherrer equation, it was determined that Lu2O3 and Eu:Lu2O3 powders presented nearly spherical particle morphology with crystallites sizes in the range of 8 to 13nm. The antioxidant assays results revealed that europium ion enhance Lu2O3 powders antioxidant properties, showing that 12.5mol% of europium is sufficient to reach its maximum capacity.

Sol-Gel Synthesis and Antioxidant Properties of Yttrium Oxide Nanocrystallites Incorporating P-123.

Yttrium oxide (Y2O3) nanocrystallites were synthesized by mean of a sol-gel method using two different precursors. Raw materials used were yttrium nitrate and yttrium chloride, in methanol. In order to promote oxygen vacancies, P-123 poloxamer was incorporated. Synthesized systems were heat-treated at temperatures from 700 °C to 900 °C. Systems at 900 °C were prepared in the presence and absence of P-123 using different molar ratios (P-123:Y = 1:1 and 2:1). Fourier transform infrared spectroscopy (FTIR) results revealed a characteristic absorption band of Y-O vibrations typical of Y2O3 matrix. The structural phase was analyzed by X-ray diffraction (XRD), showing the characteristic cubic phase in all systems. The diffraction peak that presented the major intensity corresponded to the sample prepared from yttrium chloride incorporating P-123 in a molar ratio of P-123:Y = 2:1 at 900 °C. Crystallites sizes were determined by Scherrer equation as between 21 nm and 32 nm. Antioxidant properties were estimated by 2,2-diphenyl-1-picrylhydrazyl (DPPH•) assays; the results are discussed.

Preparation of O-methyl substituted 2-oxofuro- and 2-oxopyrrolidinoindolines by reductive lactonization of oxindol-3-ylacetic acids.

A practical procedure for the preparation of O-methyl substituted 3a,8-dialkyl-2-oxofuroindolines is described. Reductive lactonization of the corresponding oxindol-3-ylacetic acids provides a route for the formation of this class of compounds. Further transformation of 2-oxofuroindolines into 2-oxopyrrolidinoindolines, and then to pyrrolidinoindolines demonstrates their versatility as key intermediates in natural products synthesis. The results of single-crystal X-ray crystallographic analyses are given for five of the studied compounds.

Unimolecular rearrangements of ketene-O,O-acetals and fragmentations occurring in the gas phase.

Gas phase skeletal rearrangements of regioisomeric 3-cyano-2-methoxy-3a-alkylfuro[2,3-b]- and [3,2-b]indoles were evidenced by product ions [M-32](+•), consistent with loss of methanol, on electron ionization in their mass spectra. The rearranged products occurring in gas phase were demonstrated to have elemental composition and fragmentation properties identical to those of authentic samples of 2-indolyl cyanomalonates. Isotopic labeling experiments support the formation mechanism of the [M-32](+•) ion. Additional thermal gas-phase reaction products were characterized by comparison with an authentic sample.

Cascade [1,3]-sigmatropic rearrangements of ketene O,O-acetals: kinetic and DFT level mechanistic studies.

The regioisomeric alpha-cyano ketene-O,O-dialkyl acetals 2a-e and 4a-e, sequential intermediates in the diazomethane induced conversion of indole alpha-cyano-gamma-lactones 1a-e to 2-indolyl cyanomalonates 5a-e, were isolated and characterized. Formation of the steady-state intermediate cycloprop[b]indoles 3a-e was evidenced by means of NMR and confirmed by the X-ray structure of 3c, demonstrating that the formation of 5a-e from 2a-e proceeds through two consecutive and one parallel unimolecular steps, with intermediates 3a-e formed in reversible processes. Evidence that the reversible reactions proceed via [1,3]-rearrangements is presented. The steady-state kinetic approach applied to intermediate 3 allowed a minimal two consecutive step 2 --> 4--> 5 kinetic model, in which the steric bulkiness of the alkyl substituent affects strongly the associated rate constants, k(1) and k(2), inverting the rate-determining step. The solvation effects enhanced the feasibility of these skeletal rearrangements as they stabilized the transition states to a great extent. The experimental determined thermodynamic parameters and DFT calculations suggest that these cascade rearrangements occur through [1,3]-sigmatropic mechanisms, in which asynchronous bond reorganization processes via four membered pseudopericyclic transition states are highly favorable.