Anti-toxoplasma activity and DNA-binding of copper(II) and zinc(II) coordination compounds with 5-nitroimidazole-based ligands.

Tetrahedral copper(II) and zinc(II) coordination compounds from 5-nitroimidazole derivatives, viz. 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (cenz) and ornidazole 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (onz), were synthesized and spectroscopically characterized. Their molecular structures were determined by X-ray diffraction studies. The complexes [Cu(onz)2X2], [Zn(onz)2X2], [Cu(cenz)2X2] and [Zn(cenz)2X2] (X- = Cl, Br), are stable in solution and exhibit positive LogD7.4 values that are in the range for molecules capable of crossing the cell membrane via passive difussion. Their biological activity against Toxoplasma gondi was investigated, and IC50 and lethal dose (LD50) values were determined. The ornidazole copper(II) compounds showed very good antiparasitic activity in its tachyzoite morphology. The interaction of the coordination compounds with DNA was examined by circular dichroism, fluorescence (using intercalating ethidium bromide and minor groove binding Hoechst 33258) and UV-Vis spectroscopy. The copper(II) compounds interact with the minor groove of the biomolecule, whereas weaker electrostatic interactions take place with the zinc(II) compounds. The spectroscopic data achieved for the two series of complexes (namely with copper(II) and zinc(II) as metal center) agree with the respective DNA-damage features observed by gel electrophoresis.

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.

Evaluation of genotoxic damage, production reactive oxygen and nitrogen species in Plasmodium yoelii yoelii exposed to sodium metavanadate.

Malaria represents the greatest global health burden among all parasitic diseases, with drug resistance representing the primary obstacle to control efforts. Sodium metavanadate (NaVO3) exhibits antimalarial activity against the Plasmodium yoelii yoelii (Pyy), yet its precise antimalarial mechanism remains elusive. This study aimed to assess the antimalarial potential of NaVO3, evaluate its genotoxicity, and determine the production of reactive oxygen and nitrogen species (ROS/RNS) in Pyy. CD-1 mice were infected and divided into two groups: one treated orally with NaVO3 (10 mg/kg/day for 4 days) and the other untreated. A 50% decrease in parasitemia was observed in treated mice. All experimental days demonstrated DNA damage in exposed parasites, along with an increase in ROS and RNS on the fifth day, suggesting a possible parasitostatic effect. The results indicate that DNA is a target of NaVO3, but further studies are necessary to fully elucidate the mechanisms underlying its antimalarial activity.

Changes in the Proliferation of the Neural Progenitor Cells of Adult Mice Chronically Infected with Toxoplasma gondii.

During Toxoplasma gondii chronic infection, certain internal factors that trigger the proliferation of neural progenitor cells (NPCs), such as brain inflammation, cell death, and changes in cytokine levels, are observed. NPCs give rise to neuronal cell types in the adult brain of some mammals. NPCs are capable of dividing and differentiating into a restricted repertoire of neuronal and glial cell types. In this study, the proliferation of NPCs was evaluated in CD-1 adult male mice chronically infected with the T. gondii ME49 strain. Histological brain sections from the infected mice were evaluated in order to observe T. gondii tissue cysts. Sagittal and coronal sections from the subventricular zone of the lateral ventricles and from the subgranular zone of the hippocampal dentate gyrus, as well as sagittal sections from the rostral migratory stream, were obtained from infected and non-infected mice previously injected with bromodeoxyuridine (BrdU). A flotation immunofluorescence technique was used to identify BrdU+ NPC. The scanning of BrdU+ cells was conducted using a confocal microscope, and the counting was performed with ImageJ® software (version 1.48q). In all the evaluated zones from the infected mice, a significant proliferation of the NPCs was observed when compared with that of the control group. We concluded that chronic infection with T. gondii increased the proliferation of NPCs in the three evaluated zones. Regardless of the role these cells are playing, our results could be useful to better understand the pathogenesis of chronic toxoplasmosis.

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.

Bioactive Peptides against Human Apicomplexan Parasites.

Apicomplexan parasites are the causal agents of different medically important diseases, such as toxoplasmosis, cryptosporidiosis, and malaria. Toxoplasmosis is considered a neglected parasitosis, even though it can cause severe cerebral complications and death in immunocompromised patients, including children and pregnant women. Drugs against Toxoplasma gondii, the etiological agent of toxoplasmosis, are highly toxic and lack efficacy in eradicating tissue cysts, promoting the establishment of latent infection and acute relapsing disease. Cryptosporidiosis has been recognized as the most frequent waterborne parasitosis in US outbreaks; anti-cryptosporidium drug discovery still faces a major obstacle: drugs that can act on the epicellular parasite. Severe malaria is most commonly caused by the progression of infection with Plasmodium falciparum. In recent years, great progress has been made in the field of antimalarial drugs and vaccines, although the resistance of P. falciparum to artemisinin has recently gained a foothold in Africa. As seen, the search for new drugs against these parasites remains a challenge. Peptide-based drugs seem to be attractive alternative therapeutic agents recently recognized by the pharmaceutical industry, as they can kill different infectious agents and modulate the immune response. A review of the experimental effects of bioactive peptides on these parasites follows, along with comments. In addition, some biological and metabolomic generalities of the parasites are reviewed to elucidate peptide mechanisms of action on Apicomplexan targets.

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.