Antiparasitic Properties Research Articles

Chemical Prospection of Qualea grandiflora Mart. Fruit and Stem Extracts and Their in vitro and in vivo Antiplasmodial Activity

Qualea grandiflora Mart. (“pau-terra”) is a medicinal plant symbolic from Cerrado biome. Qualea species reportedly have antiparasitic properties, but their active compounds have yet to be identified. In this study, we investigated the antiplasmodial activity of Q. grandiflora fruit and stem extracts against Plasmodium falciparum. The polar extracts of both fruits and stems showed promising in vitro antiplasmodial activity against sensitive and resistant P. falciparum strains (half-maximal inhibitory concentration (IC50) = 1.2 and 4.2 ng mL-1, respectively), low cytotoxicity against human hepatic cells (IC50HepG2 ≥ 400 ng mL-1), and a noteworthy selectivity index (SI ≥ 322 and ≥ 96, respectively). The fruit ethanolic extract revealed significant oral efficacy at 100 mg kg-1 in a mouse model of P. berghei malaria (100% reduction in parasitemia on day 5 post-infection). To investigate the chemical composition of the extracts, we developed a method involving liquid chromatography-high resolution quadrupole-time of flight mass spectrometer. The chemical profiling of active extracts indicated 32 compounds, including gallotannins, ellagic acid derivatives and flavonoids. The common component in the active polar extracts was found to be ellagic acid (EA), which may contribute favorably to the in vitro and in vivo inhibitory activity observed in this study.

Review of the use of gentian violet in dermatology practice

To review the use of gentian violet in dermatology. A comprehensive literature search on gentian violet in dermatology practice was performed through PubMed. Gentian violet is effective in treating methicillin-resistant Staphylococcus aureus-colonized skin lesions; mean number of days for complete eradication was 9.1 days. Gentian violet is almost as effective as ketoconazole and more effective than nystatin in the treatment of oral thrush in AIDS patients. In an in vitro study on cutaneous T cell lymphoma cell lines, there was no difference between nitrogen mustard and gentian violet in stimulating apoptosis. When comparing gentian violet to silver sulfadiazine dressings in healing burn wounds, the gentian violet treatment group reported less pain, fewer febrile episodes, and decreased bacterial growth compared to control. In atopic dermatitis subjects, gentian violet decreased Staphylococcus aureus colonization and improved disease severity in lesional skin compared to non-lesional skin. Studies have investigated gentian violet's antibacterial, antifungal, antiviral, antiparasitic, anti-angiogenic, antitumor, and wound healing properties. Gentian violet is a low cost and well-tolerated topical agent with the potential for widespread applications in dermatology.

One-pot Synthesis of Betulin Triterpenoid Quaternized Pyridine Derivatives and their Antimicrobial Activity

Background: A wide range of biological activity, relatively low toxicity and multiple pharmacological effects of triterpenoids are major advantages of these compounds in the prevention and treatment of various diseases. They include the lupane- type triterpenoids that proved to be a promising platform for the synthesis of analogs with a wide range of biological activities, including anti-inflammatory, antitumor, antiparasitic and antiviral properties. The main disadvantage complicating the use of all known derivatives of lupane acids in medical practice is low bioavailability associated with poor solubility in biologic fluids, limiting their effective interaction with the biological targets. Objective: The objective of this study is the synthesis of new amphiphilic betulin derivatives on the base of pyridinium salts with antifungal and antibacterial activity. Methods: In this study we have developed an effective one-pot method for the preparation of new quaternized pyridine derivatives 4-6 of the betulinic series based on the reaction of the initial triterpenes 1-3 with the Tempo+Br3 - reagent in the pyridine. The synthesized and initial compounds were tested for their antimicrobial and antifungal activity. Results: The data presented in this document indicate that all synthesized compounds 4-6 exhibited high activity against both gram-positive Staphylococcus aureus bacteria and gram-negative Pseudomonas aeruginosa strains, as well as Candida albicans and Cryptococcus neoformans fungi with the >90% coverage of the inhibition zone. The best result in a series of compounds 4-6 was found for the derivative 6 at the minimum inhibitory concentration of 1 µg/ml against S. aureus bacteria, C. albicans and C. neoformans fungi at the concentration of 8 µg/ml. Conclusion: Thus, we have demonstrated the first example of the pyridine quaternization using the betulin triterpenoids as the lipophilic substrates and Tempo+Br3 - cation. The obtained quaternized pyridine analogs of betulin triterpenes showed high antibacterial and antifungal activity in comparison with the initial compounds.

259 Screening of Lespedeza germplasm for forage quality and bioactivity

Abstract Interest in the condensed tannin-containing legume sericea lespedeza (Lespedeza cuneata) as a nutraceutical (bioactive) forage for livestock has been increasing in the United States but other Lespedeza species have not been adequately evaluated. A study was completed to determine the nutritional and bioactivity potential of Lespedeza species obtained from the USDA Plant Genetic Resources Conservation Unit in Griffin, GA. Accessions from 15 Lespedeza species were planted in small plots at Fort Valley State University in Fort Valley, GA. After establishment, forage was harvested, freeze-dried, ground and analyzed for neutral detergent fiber (NDF), acid detergent fiber (ADF), in vitro true digestibility (IVTD), total phenolics (TP), and protein precipitable phenolics (PPP). Species differences were significant (P < 0.01) for all parameters measured. Lespedeza cuneata accessions, including “AUGrazer,” the cultivar most commonly used as an anti-parasitic crop in the United States had NDF, ADF, and IVTD values of 35.7±0.4%, 26.8±0.4%, and 74.3±1.2%, while L. virginica, a native species, had 34.9±3.0%, 26.0±2.5%, and 74.9±4.2%, respectively. The L. cuneata accessions averaged 179.6±4.3 and 133.6±3.5 mg/g of forage material for TP and PPP, while L. virginica averaged 564.2±24.6 and 306.5±19.9 mg/g, respectively. Other species varied from 30.5±3.0 to 47.4±4.2% NDF, 22.9±1.6 to 36.4±3.6% ADF, 55.2±5.9 to 81.6±3.4% IVTD, and 107.7±17.4 to 283.5±34.7 and 55.2±14.0 to 139.4±28.1 mg/g of forage for TP and PPP, respectively. Based upon these results, Lespedeza species tested in this study, particularly L. virginica, have potential as nutraceutical forages for livestock production systems. As L. cuneata accessions established and grew much better than other Lespedeza species in this study, agronomic testing of this germplasm collection in other environments is warranted. In addition, determining potential anti-parasitic properties of these species using in vitro and in vivo testing would be beneficial.

Anti-protozoal activity of extracts from chicory (Cichorium intybus) against Cryptosporidium parvum in cell culture

Cryptosporidium spp. are responsible for severe public health problems and livestock production losses. Treatment options are limited to only one drug available for human and bovine cryptosporidiosis, respectively, and both drugs exhibit only partial efficacy. Sesquiterpene lactones (SL) are plant bioactive compounds that function as a defence mechanism against herbivores. SL have demonstrated anti-parasitic properties against a range of parasitic taxa but knowledge about their anti-Cryptosporidium efficacy is limited. The effect of SL-rich leaf and root extracts from chicory (Cichorium intybus cv. Spadona) was investigated using human colon adenocarcinoma (HCT-8) cells infected with Cryptosporidium parvum. C. parvum oocysts were inoculated onto the cell monolayer and i) incubated for 4 hours with extracts (leaf and root extracts 300, 150, 75, 37.5, 18.75 and 9.375 μg/mL) in triplicates followed by incubation in bioactive free media (sporozoite invasion assays) or ii) incubated for 4 hours in bioactive free media followed by 48-hours incubation with extracts (growth inhibition assays). Extract toxicity on HCT-8 cells was assessed via water-soluble tetrazolium (WST)-1 assay prior to quantifying parasitic growth via immunofluorescence. Both extracts demonstrated dose-dependent inhibition in the growth inhibition assays (p = < 0.0001 for both extracts) but not in the invasion assays. Anti-parasitic activity did not appear to be solely related to SL content, with the extract with lower SL content (leaf) exhibiting higher inhibition at 300 μg/ml. However, given the limited treatment options available for Cryptosporidium spp., our study encourages further investigation into the use of chicory extracts to identify novel active compound(s) inhibiting these protozoa.

Liposoluble compounds from Ganoderma lipsiense grown on solid red rice medium with antiparasitic and antibacterial properties.

Liposoluble molecules are a group of compounds that display potent biological and therapeutic properties. The present study aimed to identify liposoluble molecules produced by Ganoderma lipsiense grown in red rice medium using solid-state fermentation (SSF) techniques, and to investigate the antigiardial and antibacterial activities potential of extracts in vitro. Eighteen fatty acids and derivatives were identified by gas chromatograph-mass spectrometry (GC-MS) analysis in G. lipsense extract. Qualitative (Fourier transform infrared spectroscopy and nuclear magnetic resonance) characterizations identified the steroid ergosta-6,22-diene-3β,5α,8α-triol in purified hexane subfraction (HEXsf) F19 isolated from hexane fraction (HEXf) of crude extract (CE). Ergosta-6,22-diene-3β,5α,8α-triol exhibited significant inhibitory activity against Giardia duodenalis throphozoites (93.6%) in in vitro assays. CE and HEXf inhibited 95.38% and 92.74% of the G. duodenalis throphozoites in 100µg mL-1 , whereas CE and their fractions dichloromethane (DCMf) and ethyl acetate (EAf) showed antibacterial activities against Pseudomonas aeruginosa and Staphylococcus aureus at 500µg mL-1 . Importantly, some liposoluble compounds produced and identified in G. lipsiense are unpublished for this species. This is first report for the production of ergosta-6,22-diene-3β,5α,8α-triol by G. lipsiense and its antiparasitic activity.

Enantioselective synthesis and anti-parasitic properties of aporphine natural products

Chagas disease and visceral leishmaniasis are neglected protozoan diseases with significant impact in developing countries. Due to the limited number and toxicity of current therapies, new drug leads are urgently needed. In this work, four aporphine natural products were synthesized using an enantioselective, modular and convergent strategy, comprising eight steps in the longest linear sequence; key steps included Bischler-Napieralski cyclization/Noyori asymmetric reduction to construct the tetrahydroisoquinolines, and palladium-catalyzed arylation to close the C ring. Norglaucine, nordicentrine and dicentrine showed promising bioactivity against T. cruzi and L. infantum, suggesting potential for further development of these scaffolds as antiparasitic agents.

Anthelmintic herbal extracts as potential prophylactics or treatments for monogenean infections in cultured yellowtail kingfish (Seriola lalandi)

Monogenean parasites pose a considerable threat to the aquaculture of yellowtail kingfish, Seriola lalandi. Current chemotherapeutic treatments are expensive, labor intensive and can cause mortality if incorrectly administered. Many medicinal herbs possess anti-parasitic properties and therefore have potential as an alternative or supplement to current treatment methods. The anthelminthic effects of garlic, rosemary, and commercially manufactured herbal products were trialed both in vitro and in vivo against two species of monogeneans, Neobenedenia girellae and Zeuxapta seriolae, to assess their suitability for use in yellowtail kingfish aquaculture. The survival of adult N. girellae and Z. seriolae and larval N. girellae (i.e. oncomiracidia) were assessed in vitro, by exposure to seawater solutions containing the herbal products. All herbal-seawater solutions significantly reduced the survival of mature N. girellae and Z. seriolae and N. girellae oncomiracidia relative to the controls. Two in vivo trials were then conducted to examine the preventative and curative treatment effects of rosemary and garlic against Z. seriolae infections, by supplementing these products into their feed. The first trial fed supplemented diets for 30 days prior to exposure with Z. seriolae oncomiracidia. The second trial examined the potential curative effects of these extracts by feeding supplemented diets to yellowtail kingfish already infected with Z. seriolae for 10 and 20 days. The effect of these curative treatment diets on recruitment of juvenile Z. seriolae was also assessed. Supplementation of rosemary and garlic products into feed 30 days prior to experimental exposure significantly reduced Z. seriolae infection success, while supplementation of garlic powder, rosemary extract, and rosemary oil onto pellets significantly reduced Z. seriolae abundance on yellowtail kingfish after 20 days of feeding. Recruitment of juvenile Z. seriolae was also significantly reduced.

Promethazine exhibits antiparasitic properties in vitro and reduces worm burden, egg production, hepato-, and splenomegaly in a schistosomiasis animal model.

The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 μM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent.

Chagas Disease Drug Discovery: Multiparametric Lead Optimization against Trypanosoma cruzi in Acylaminobenzothiazole Series.

Acylaminobenzothiazole hits were identified as potential inhibitors of Trypanosoma cruzi replication, a parasite responsible for Chagas disease. We selected compound 1 for lead optimization, aiming to improve in parallel its anti-T. cruzi activity (IC50 = 0.63 μM) and its human metabolic stability (human clearance = 9.57 mL/min/g). A total of 39 analogues of 1 were synthesized and tested in vitro. We established a multiparametric structure-activity relationship, allowing optimization of antiparasite activity, physicochemical parameters, and ADME properties. We identified compound 50 as an advanced lead with an improved anti-T. cruzi activity in vitro (IC50 = 0.079 μM) and an enhanced metabolic stability (human clearance = 0.41 mL/min/g) and opportunity for the oral route of administration. After tolerability assessment, 50 demonstrated a promising in vivo efficacy.

Assessment of the potential therapeutic effects of omeprazole in Schistosoma mansoni infected mice.

Schistosomiasis is a neglected chronic parasitic disease with a significant lasting morbidity. Currently, praziquantel (PZQ) is the most efficient drug for schistosomiasis worldwide. However, the possibility of the occurrence of resistance to PZQ is increasing. Therefore, there is a vital need to find new antischistosomal drugs or to increase the efficacy of the existing ones. Omeprazole is a proton pump inhibitor which is reported to have antiparasitic properties. Thus, the aim of this study was to assess the potential therapeutic effects of omeprazole in experimental Schistosoma mansoni infection either alone or in combination with PZQ. For this aim, 80 laboratory bred mice were divided into 3 groups; uninfected control, infected untreated control, and infected and treated at tenth week P.I. The last group was divided into three subgroups that received either PZQ alone, omeprazole alone, or both drugs. The effectiveness of treatment was assessed by adult worm counts, liver egg count, scanning electron microscopy of adult worms, histopathological, and immunohistochemical (GFAP) examination. There was significant reduction of adult worm counts, liver egg counts, size, diameter of hepatic granulomas, hepatic fibrosis, and GFAP expression in the group that received combined treatment as compared to PZQ group. Moreover, the tegumental changes were more evident in the group that received combined treatment. In conclusion, the administration of omeprazole with PZQ improved the efficacy of PZQ in the treatment of Schistosomiasis mansoni.

Antiparasitic activity of the medicinal plant Dillenia suffruticosa against the marine leech Zeylanicobdella arugamensis (Hirudinea) and its phytochemical composition

Zeylanicobdella arugamensis (Annelida: Hirudinea), a marine parasitic leech, is currently affecting different species of cultured groupers, hybrid groupers, snappers and sea bass in Malaysia. Dillenia suffruticosa (Dilleniaceae), a medicinal plant found in Sabah, has been selected in our experiment to kill the leeches as a natural control method. The leech-infested hybrid groupers were collected from aquaculture facilities, and the isolated leeches were challenged against methanol extract of D. suffruticosa leaves. The experiment was carried out using various concentrations of the extracts such as 25, 50 and 100 mg/ml. The methanol extract showed significant antiparasitic activity against Z. arugamensis with 100% mortality at a concentration of 100 mg/ml in 14.39 ± 3.75 min., followed by 50 and 25 mg/ml in 32.97 ± 9.29 and 41.77 ± 5.40 min., respectively. The phytochemical composition of the extract was determined using GC-MS analysis to understand the nature of the principal compounds responsible for its antiparasitic properties. The leaves of D. suffruticosa demonstrated the presence of different bioactive compounds of various natures with varying percentages. Thus, it could be revealed that the methanol extract of D. suffruticosa mainly contains vital phytochemical compounds and showed an effective antiparasitic activity against the harmful leeches of hybrid groupers.

Chemical Composition and Biological Activities of Artemisia pedemontana subsp. assoana Essential Oils and Hydrolate.

Given the importance of the genus Artemisia as a source of valuable natural products, the rare plant Artemisia pedemontana subspecies assoana, endemic to the Iberian Peninsula, has been experimentally cultivated in the greenhouse and aeroponically, to produce biomass for essential oil (EO) extraction. The chemical composition of the EOs was analyzed, and their plant protection (insects: Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae; plants: Lactuca sativa and Lolium perenne; fungi: Aspergillus niger; and nematode: Meloidogyne javanica) and antiparasitic (Trypanosoma cruzi, Phytomonas davidi, and antiplasmodial by the ferriprotoporphyrin biocrystallization inhibition test) properties were studied, in addition to the hydrolate by-product. The EOs showed a 1,8-cineole and camphor profile, with quantitative and qualitative chemical differences between the cultivation methods. These oils had moderate insect antifeedant, antifungal, and phytotoxic effects; were trypanocidel; and exhibited moderate phytomonacidal effects, while the hydrolate showed a strong nematicidal activity. Both EOs were similarly antifeedant; the EO from the greenhouse plants (flowering stage) was more biocidal (antifungal, nematicidal, and phytotoxic) than the EO from the aeroponic plants (growing stage), which was more antiparasitic. The major components of the oils (1,8-cineole and camphor), or their 1:1 combination, did not explain any of these effects. We can conclude that these EOs have potential applications as insect antifeedants, and as antifungal or antiparasitic agents, depending on the cultivation method, and that the hydrolate byproduct is a potent nematicidal.

Antitumor and anti-nematode activities of α-mangostin

α-Mangostin, one of the major xanthones isolated from pericarp of mangosteen (Garcinia mangostana Linn), exhibits a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial as well as anticancer, both in in vitro and in vivo studies. In the present study, α-mangostin' anti-cancer and anti-parasitic properties were tested in vitro against three human cell lines, including squamous carcinoma (SCC-15) and glioblastoma multiforme (U-118 MG), compared to normal skin fibroblasts (BJ), and in vivo against Caenorhabditis elegans. The drug showed cytotoxic activity, manifested by decrease of cell viability, inhibition of proliferation, induction of apoptosis and reduction of adhesion at concentrations lower than 10 μM (the IC50 values were 6.43, 9.59 and 8.97 μM for SCC-15, U-118 MG and BJ, respectively). The toxicity, causing cell membrane disruption and mitochondria impairment, was selective against squamous carcinoma with regard to normal cells. Moreover, for the first time anti-nematode activity of α-mangostin toward C. elegans was described (the LC50 = 3.8 ± 0.5 μM), with similar effect exerted by mebendazole, a well-known anthelmintic drug.

Activation of Mast Cells Promote Plasmodium berghei ANKA Infection in Murine Model.

Malaria, a mosquito-borne infectious disease, is a severe health problem worldwide. As reported, some anti-malarial drugs with anti-parasitic properties also block mast cells (MCs) activities. It is hypothesized that MCs activity may be correlated with the pathogenesis of malaria. Thus, the role of MCs on malarial pathogenesis and the involved physiological action and pathways need to be further investigated. This study aimed to investigate the effect of MCs activation on malaria disease severity using KunMing mice with Plasmodium berghei ANKA (PbANKA) infection treated with MCs degranulator (compound 48/80, C48/80) or MCs stabilizer (disodium cromoglycate, DSCG). PbANKA infection caused a dramatic increase in MCs density and level of MCs degranulation in cervical lymph node (CLN) and skin. Compared with infected control, C48/80 treatment had shortened survival time, increased parasitemia, exacerbated liver inflammation and CLN hyperplasia, accompanied with increase in vascular leakage and leukocyte number. The infected mice with C48/80 treatment also elevated the release of CCL2, CXCL1, and MMP-9 from MCs in CLN and skin, and TNF-α, IFN-γ, CCR2, and CXCR2 mRNA expression in CLN and liver. In contrast, the infected mice treated with DSCG showed longer survival time, lower parasitemia, improved liver inflammation and CLN hyperplasia, followed by a decline of vascular leakage and leukocyte number. Decreased MCs-derived CCL2, CXCL1, and MMP-9 from CLN and skin, mRNA expression in CLN and liver (TNF-α, IFN-γ, CCR2, and CXCR2) were also observed in infected mice with DSCG treatment. Our data indicated that MCs activation may facilitate the pathogenesis of PbANKA infection.

Potential use of 13-mer peptides based on phospholipase and oligoarginine as leishmanicidal agents

Phospholipase A2 toxins present in snake venoms interact with biological membranes and serve as structural models for the design of small peptides with anticancer, antibacterial and antiparasitic properties. Oligoarginine peptides are capable of increasing cell membrane permeability (cell penetrating peptides), and for this reason are interesting delivery systems for compounds of pharmacological interest. Inspired by these two families of bioactive molecules, we have synthesized two 13-mer peptides as potential antileishmanial leads gaining insights into structural features useful for the future design of more potent peptides. The peptides included p-Acl, reproducing a natural segment of a Lys49 PLA2 from Agkistrodon contortrix laticinctus snake venom, and its p-AclR7 analogue where all seven lysine residues were replaced by arginines. Both peptides were active against promastigote and amastigote forms of Leishmania (L.) amazonensis and L. (L.) infantum, while displaying low cytotoxicity for primary murine macrophages. Spectrofluorimetric studies suggest that permeabilization of the parasite's cell membrane is the probable mechanism of action of these biomolecules. Relevantly, the engineered peptide p-AclR7 was more active in both life stages of Leishmania and induced higher rates of ethidium bromide incorporation than its native template p-Acl. Taken together, the results suggest that short peptides based on phospholipase toxins are potential scaffolds for development of antileishmanial candidates. Moreover, specific amino acid substitutions, such those herein employed, may enhance the antiparasitic action of these cationic peptides, encouraging their future biomedical applications.

Immunomodulatory and Antimicrobial Effects of Vitamin C.

Humans have lost their vitamin C-synthesizing capacities during evolution. Therefore, the uptake of this essential compound from external sources is mandatory in order to prevent vitamin C-deficient conditions resulting in severe morbidities such as scurvy. The potent antioxidant, immunomodulatory, and antiinfectious effects of vitamin C are known since the 1930s. We here (i) review the impact of vitamin C on innate and adaptive immune functions, (ii) provide an overview of its antimicrobial, antibacterial, antiviral, antiparasitic, and antifungal properties, and finally, (iii) discuss vitamin C as an adjunct treatment option for the combat of human infections by bacteria, particularly by emerging multidrug-resistant species.

Effect of curcuminoids and curcumin derivate products on thioredoxin-glutathione reductase from Taenia crassiceps cysticerci. Evidence suggesting a curcumin oxidation product as a suitable inhibitor.

Curcuma is a traditional ingredient of some Eastern cuisines, and the spice is heralded for its antitumoral and antiparasitic properties. In this report, we examine the effect of the curcuminoides which include curcumin, demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC), as well as curcumin degradation products on thioredoxin glutathione reductase from Taenia crassiceps cysticerci Results revealed that both DMC and BDMC were inhibitors of TGR activity in the micromolar concentration range. By contrast, the inhibitory ability of curcumin was a time-dependent process. Kinetic and spectroscopical evidence suggests that an intermediary compound of curcumin oxidation, probably spiroepoxide, is responsible. Preincubation of curcumin in the presence of NADPH, but not glutathione disulfide (GSSG), resulted in the loss of its inhibitory ability, suggesting a reductive stabilizing effect. Similarly, preincubation of curcumin with sulfhydryl compounds fully protected the enzyme from inhibition. Degradation products were tested for their inhibitory potential, and 4-vinylguaiacol was the best inhibitor (IC50 = 12.9 μM), followed by feruloylmethane (IC50 = 122 μM), vanillin (IC50 = 127 μM), and ferulic aldehyde (IC50 = 180 μM). The acid derivatives ferulic acid (IC50 = 465 μM) and vanillic acid (IC50 = 657 μM) were poor inhibitors. On the other hand, results from docking analysis revealed a common binding site on the enzyme for all the compounds, albeit interacting with different amino acid residues. Dissociation constants obtained from the docking were in accord with the inhibitory efficiency of the curcumin degradation products.

Effect of Fluorination on the Structure and Anti-Trypanosoma cruzy Activity of Oxorhenium(V) Complexes with S,N,S-Tridentate Thiosemicarbazones and Benzoylthioureas. Synthesis and Structures of Technetium(V) Analogues.

A series of 16 "3 + 2" mixed-ligand complexes of the general composition [ReO(L1)(L2)] (H2L1a-H2L1d = tridentate thiosemicarbazones having a phenyl group with 4-H, 4-F, 3,5-di-F, and 4-CF3 substituents; HL2a-HL2d = bidentate N,N-diethyl-N'-benzoylthioureas with 4-H, 4-F, 3,5-di-F, and 4-CF3 substituents at the benzoyl groups) have been synthesized and characterized by spectroscopic methods and X-ray diffraction. Irrespective of the individual fluorine substitution, the complexes are stable and possess the same general structure. Some systematic electronic effects of the fluorine-substitution patterns of the ligands have been found on the 13C NMR chemical shifts of the N-C═N carbon atoms of the {L1}2- and the C═O carbon atoms of the {L2}- ligands. Antiparasitic properties of the rhenium complexes have been tested against epimastigotes and trypomastigotes forms of two Trypanosoma cruzi strains and the amastigotes form of one of them. The results of this study indicate that the activity of the rhenium complexes can clearly be modulated by fluorine substitution of their ligands. Some of the fluorinated compounds show a high activity against epimastigotes and trypomastigotes forms of the parasites. Reactions between (NBu4)[TcOCl4] and two representatives of the fluorinated ligands (H2L1b, 4-F-substituted, and H2L1c, 4-CF3-substituted) form stable complexes of the composition [TcOCl(L1b)] and [TcOCl(L1c)]. Subsequent reactions of these products with HL2b (4-F-substituted) give the corresponding [TcO(L1)(L2)] mixed-ligand complexes. Also, the technetium compounds are stable as solids and in solutions and have structures corresponding to those of their rhenium analogues.

Medicinal Plants with anti-Acanthamoeba Activity: A Systematic Review.

Recently, herbal medicine has received much attention in the literature. Several essential oils or plant extracts have been found to have anti-Acanthamoeba properties against trophozoites and cysts of Acanthamoeba spp. The aim of this systematic review is to introduce anti-Acanthamoeba properties of some essential oils or plant extracts; perhaps the results of this research will be used to prevent and treat infectious diseases. All published papers in English and Persian databases were systematically searched for some specific keywords to find articles that have influenced plant compounds on Acanthamoeba up to April 2018. Articles related to the subject were selected and studied. A total of 51 articles including 136 experiments (128 in vitro and 8 in vivo) between 1999 and 2018, met our eligibility criteria. Totally, 110 species of plants belonging to 34 families, mainly Lamiaceae (15 plant species) and Asteraceae (13 plant species) were studied against trophozoites and cysts of Acanthamoba in in vitro and in vivo. Most of the plant's species were Citrus (6 species), Allium (5 species), Peucedanum, Piper, Lippia, and Olive (4 species). The most frequently used parts were leaves, aerial parts, flowers, bark, rhizomes, and seeds. Recent studies have shown that many natural compounds have high anti-parasitic properties and low toxicity. Our research team hopes that the information provided in present systematic review can improve new experimental and clinical trials and herbal combination therapy. Further studies are needed to understand the molecular mechanisms in the anti-amoebic reactions of plant species and ocular toxicity of extracts in animal models.