Antiparasitic Activity Research Articles

INDIAN COSTUS IN ISLAMIC, AYURVEDA, TCM AND MODERN MEDICINE, A REVIEW ON ANTIMICROBIAL ACTION

Indian Costus species has been mentioned as an herbal remedy for infections in Islamic, Ayurveda and Traditional Chinese Medicine (TCM) literature as well. Using the Indian costus to treat disease is one of the cross-cultural practices, just like cupping therapy and meditation. This would mean that it is safe and beneficial. In the saying (Hadith) of the prophet of Islam, it was prescribed to treat pharyngitis and pleurisy (Ahmad et al., 2009). In TCM, Costus root (Guang Mu Xiang) powder is used to treat gastroenteritis and tenesmus (Nystrom, 2015). In Ayurveda, it is used as a spasmolytic and antiparasitic for intestinal disease (Pandey et al., 2007). Among the pharmacological benefits of costus is the antimicrobial effect. This includes the antibacterial, antiviral, antifungal and antiparasitic action of the substances to be discussed here. We did a focus on the antimicrobial effect in the three systems, compared and concluded findings through modern medicine to verify the evidence here.

Green Synthesis of Uncoated and Olive Leaf Extract-Coated Silver Nanoparticles: Sunlight Photocatalytic, Antiparasitic, and Antifungal Activities.

The circular economy, which attempts to decrease agricultural waste while also improving sustainable development through the production of sustainable products from waste and by-products, is currently one of the main objectives of environmental research. Taking this view, this study used a green approach to synthesize two forms of silver nanoparticles: coated silver nanoparticles with olive leaf extract (Ag-olive) and uncoated pure silver nanoparticles (Ag-pure), which were produced by the calcination of Ag-olive at 550 °C. The extract and the fabricated nanoparticles were characterized by a variety of physicochemical techniques, including high-performance liquid chromatography (HPLC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Adult ticks (Hyalomma dromedarii) (Acari: Ixodidae) were used in this study to evaluate the antiparasitic activity of synthesized nanoparticles and extract. Furthermore, the antifungal activity was evaluated against Aspergillus aculeatus strain N (MW958085), Fuserium oxysporum (MT550034), and Alternaria tenuissiuma (MT550036). In both antiparasitic and antifungal tests, the as-synthesized Ag-olive showed higher inhibition activity than Ag-pure and olive leaf extract. The findings of this research suggest that Ag-olive may be a powerful and eco-friendly antiparasitic and antifungal agent. Ag-pure was also evaluated as a photocatalyst under sunlight for the detoxification of Eri-chrome-black T (EBT), methylene blue (MB), methyl orange (MO), and rhodamine B (RhB).

DFT Calculations, Pro-Apoptotic Effects, and Anti-Infective Investigations of Alkaloids Isolated from the Stem Bark Extract of Enantia chlorantha

Fractionation of the stem bark of Enantia chlorantha Oliv yields three alkaloids, palmatine (1), jatrorrhizine (2), columbamine (3), and β-Sitosterol (4). In this investigation, density functional theory (DFT) calculations were carried out to evaluate the electronic structure and properties of 1–4 by DFT-B3LYP/6-31G level of theory using Gaussian 09 software. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), HOMO-LUMO energy difference (band gap), hardness (η), softness (S), dipole moment (μ), electronegativity (χ), hydrophobicity (logP), topological surface area (TPSA), and energy gap (Eg) were calculated. The in vitro cytotoxicity of the compounds was investigated against MCF-7 and HCT116 cancer cell lines using Wi-38 cells as a control. The compounds inhibited the proliferation of the MCF-7 and HCT116 cell lines and induced apoptosis via upregulation of caspase-3, Bax, PARP cleavage, and downregulation of Bcl-2. DFT analyses revealed that compounds 1 and 3 have smaller energy gaps, 0.072 and 0.071eV, respectively, with the highest dipole moments; hence, these compounds are more chemically reactive and exhibit better modulation of caspase-3 enzyme and inhibitory activities of the MCF-3 and HCT116 cell lines. The antimicrobial and antiparasitic evaluation of 1–4 showed moderate efficacy against the bacterial strains and moderate antiparasitic activity against Cichlidogyrus tilapia.

A comparative study on the chemical composition, anti-microbial, antiparasitic, and cytotoxic activities of Rhanterium adpressum Coss. & Dur. and Rhanterium suaveolens Desf. essential oils from Algeria

The aim of the present study was to evaluate and compare the chemical composition, antimicrobial, antiparasitic, and cytotoxic properties of the essential oils extracted from Rhanterium adpressum Coss. & Dur. (EORA) and Rhanterium suaveolens Desf. (EORS). The main compounds of EORA were myrcene (18.51%), α-pinene (14.36%), sabinene (13.55%), β-pinene (5.67%), and camphene (5.39%). While camphene (25.06%), α-pinene (13.14%), myrcene (9.74%), sabinene (8.27%), D-limonene (7.86%), and β-pinene (7.34%) constituted the major components of EORS. A potent antibacterial activity was also recorded against Escherichia coli with MIC = 5.72 mg/mL for EORA and MIC = 5.96 mg/mL for EORS. Concerning the antifungal effect, a remarkable efficiency was exerted against the two tested Candida albicans strains (MIC < 5.96 mg/mL) for EORS and against Candida albicans 26 (MIC = 5.72 mg/mL) for EORA. Furthermore, a promising antiparasitic ability was observed against Acanthamoeba castellanii (IC50 = 6.42±0.21 μg/mL) for EORS and against Leishmania amazonensis (IC50=9.66±1.46 μg/mL) for EORA. However, low cytotoxicity was recorded against macrophages J774-A1 (LC50 = 67.68±4.02 μg/mL) only for EORS. Based on the present findings, it may be concluded that the two tested EOs possess significant antimicrobial and antiparasitic activities with minimal cytotoxicity, so they can be used as new sources of antimicrobial and antiparasitic drugs.

Antiparasitic activity of the iron-containing milk protein lactoferrin and its potential derivatives against human intestinal and blood parasites

An iron-containing milk protein named lactoferrin (Lf) has demonstrated antiparasitic and immunomodulatory properties against a variety of human parasites. This protein has shown its capability to bind and transport iron molecules in the vicinity of the host–pathogen environment. The ability of parasites to sequester the iron molecule and to increase their pathogenicity and survival depends on the availability of iron sources. Lf protein has suggested a iron chelating effect on parasites iron and, hence, has shown its antiparasitic effect. Since the parasites have a complex life cycle and have developed drug resistance, vaccines and other treatments are a handful. Therefore, therapeutic research focusing on natural treatment regimens that target the parasite and are non-toxic to host cells is urgently needed. The antiparasitic efficacy of Lf protein has been extensively studied over the past 40 years using both in vitro and in vivo studies. This review article highlighted past important studies on Lf protein that revealed its potential antiparasitic activity against various intracellular and extracellular intestinal or blood-borne human parasites. This review article structures the role of Lf protein in its various forms, such as native, peptide, and nanoformulation, laying the groundwork for its function as an antiparasitic agent and its possible known mechanisms of action.

The anti-parasitic activity of Thymus vulgaris (Thyme): A literature review

Thyme (Thymus vulgaris) is an enduring herb belonging to the mint family, Lamiaceae. It originates from the Mediterranean region and is characterized by its small, aromatic leaves, and sturdy stem. Appreciated for its robust and delightful scent, thyme is widely embraced as a culinary herb. However, its significance extends far beyond the kitchen, as it has been utilized medicinally for centuries. This is owing to the occurrence of active compounds like thymol and carvacrol, which possess noteworthy antibacterial, antioxidant, and anti-inflammatory attributes. Throughout history, thyme has been employed in the treatment of respiratory disorders, digestive ailments, and other diseases. The main objective of this study was to conduct an extensive review of the thyme plant, encompassing its classification, historical background, geographical distribution, chemical composition, and both economic and medicinal applications, particularly emphasizing its antiparasitic properties. In conclusion, apart from its well-known culinary and medicinal uses, scientific research has indicated that thyme exhibits promising effectiveness against diverse parasites. Notably, research has shown that thyme exhibited antiprotozoal activity against protozoan parasites such as Giardia lamblia, Trichomonas vaginalis, Toxoplasma gondii, Entamoeba histolytica, and others. Specific thyme extract components have shown great activity against these parasites. Thyme also has larvicidal properties, meaning that it can kill larvae. This includes Anisakis larvae, which can cause anisakiasis in humans. Thyme essential oil has been shown to effectively eliminate these larvae, suggesting that it could be used to prevent anisakiasis. Furthermore, it has also been studied for its potential to treat hepatic coccidiosis in rabbits. Research has shown that thyme oil, along with Moringa oleifera oil, can effectively reduce the number of oocysts shed by infected rabbits and improve the clinical signs of the infection. This suggests that thyme oil may be a promising therapeutic agent for tackling hepatic coccidiosis.

Antibacterial and anthelmintic activities of Xanthium strumarium (Asteraceae) extracts

Plants of the Asteraceae family are broadly used against microorganisms pathogenic to people and animals, although their potential has not been studied completely so far. In an in vitro experiment, we tested ethanolic, ethyl-ether, and dimethyl-sulfoxide extracts from the fruits, leaves, shoots, and roots of Xanthium strumarium L. for their effects on 13 species of bacteria and larvae of 3 species of nematodes. Over-8-mm-wide growth-inhibition zones of the colonies around disks saturated with ethanolic extracts from the fruits were observed for 11 bacteria: Enterobacter cloacae, Klebsiella pneumonia ssp. rhinoscleromatis, K. pneumonia ssp. ozaenae, K. aerogenes, Salmonella enterica, Escherichia coli, Morganella morganii, Enterococcus faecalis, E. faecium, Staphylococcus aureus, and Bacillus subtilis. Ethanol extract from the leaves inhibited growth of the colonies of 10 bacteria: E. cloacae, K. pneumonia ssp. rhinoscleromatis, K. pneumonia ssp. ozaenae, S. enterica, E. coli, Proteus vulgaris, E. faecalis, E. faecium, S. aureus, and B. subtilis. Ethanol extract from the stem inhibited growth of the colonies of only 6 bacteria: K. aerogenes, E. cloacae, P. vulgaris, E. faecium, S. aureus, and B. subtilis. Ethanol extract from the root inhibited growth of 10 bacteria: E. cloacae, K. pneumonia ssp. rhinoscleromatis, K. pneumonia ssp. ozaenae, K. aerogenes, S. enterica, E. coli, Pseudomonas aeruginosa, E. faecalis, E. faecium, and S. aureus. We analyzed the effects of extracts based on ethyl ether and dimethyl sulfoxide, finding no antiparasitic activity or expressed anthelmintic properties of various extracts from the fruits, leaves, stem, and roots of X. strumarium against larvae of the nematodes Strongyloides papillosus, Haemonchus contortus, and Muellerius capillaris.

Anti-COVID Drugs (MMV COVID Box) as Leishmanicidal Agents: Unveiling New Therapeutic Horizons.

Leishmaniasis, a neglected tropical disease, poses a significant global health challenge, necessitating the urgent development of innovative therapies. In this study, we aimed to identify compounds from the COVID Box with potential efficacy against two Leishmania species, laying the foundation for future chemical development. Four promising molecules were discovered, demonstrating notable inhibitory effects against L. amazonensis and L. donovani. Our study revealed that bortezomib, almitrine, and terconazole induced a significant decrease in mitochondrial membrane potential, while the above compounds and ABT239 induced plasma permeability alterations, chromatin condensation, and reactive oxygen species accumulation, indicating early apoptosis in Leishmania amazonensis promastigotes, preventing inflammatory responses and tissue damage, thereby improving patient outcomes. Furthermore, ADME predictions revealed favorable pharmacokinetic profiles for all compounds, with bortezomib and ABT239 standing out as potential candidates. These compounds exhibited intestinal absorption, blood-brain barrier penetration (excluding bortezomib), and good drug-likeness for bortezomib and ABT239. Toxicity predictions for CYP-inhibition enzymes favored bortezomib as the safest candidate. In conclusion, our study identifies bortezomib as a promising aspirant for leishmaniasis treatment, demonstrating potent antiparasitic activity, favorable pharmacokinetics, and low toxicity. These findings emphasize the potential repurposing of existing drugs for neglected diseases and highlight the importance of the COVID Box in drug discovery against tropical diseases.

Evaluation of the antimalarial and CD4+ T-cell modulatory effects of leaf methanol extract of Phyllanthus muellerianus (Kuntze) Exell (Phyllanthaceae) in Plasmodium berghei-infected mice

Ethnopharmacological relevancePhyllanthus muellerianus (Kunze) Exell, a member of the Phyllanthaceae family, is a medicinal plant widely distributed in Africa. Decoctions from the leaves are used in Nigeria to treat fevers, convulsions, some neurological disorders and malaria. Aim of the studyThis study is to evaluate the anti-malarial properties of methanol extract of Phyllanthus muellerianus (MEPM) leaves and its ethyl acetate fraction using a murine malaria model infected with Plasmodium berghei. Additionally, we seek to investigate the potential modulatory effects of this extract and fraction on CD4+ T-cell populations in the context of malaria infection. Materials and methodsThe anti-malarial effects of the leaf methanol extract of Phyllanthus muellerianus (MEPM) were screened using three established in vivo models of anti-plasmodial screening namely the curative, suppressive and prophylactic models. The methanol extract (MEPM) was afterwards fractionated into hexane (HFPM), ethyl acetate (EAFPM), and methanol (MFPM) fractions. In the pilot anti-malarial screening of the fractions, EAFPM exhibited the best antiparasitic activity. Subsequently, EAFPM was screened for anti-malarial activity using the three models above. The effects of the MEPM and EAFPM on haematological indices (Hb and PCV) of the inoculated animals were further screened and the mean survival time (MST) of the animals was monitored. CD4+ T cells of various groups were counted before and after treatment using a flow cytometer. The EAFPM was further subjected to HPLC analysis for identification of its major compounds. ResultsThe EAFPM (100 and 200 mg/kg) elicited 88% and 93% cure respectively in the curative model, while artesunate (5 mg/kg,- the positive control) gave 87% protection. The MEPM and EAFPM also gave significant suppression of parasitemia in the suppressive model. The treated groups survived beyond 28 days as against 11 days by the control group (infected but not treated). The treated groups also prevented anaemia seen in the negative control. The EAFPM group significantly modulated the CD4+ T cell.Compounds identified were Gallocatechin, Quercetin -3-O-gallate, Ellagic acid, and Methylellagic acid rhamnoside). ConclusionThe study established that the leaf of Phyllanthus muellerianus possesses antimalarial activity, thus lending support to its use in the folkloric treatment of malaria.

Investigation of studies involving the prospection of chemical compounds with antioxidant and antimicrobial potential from maytenus guianensis Klotzsch Ex Reissek in the north region: a brief review

Among the members of the Celastraceae family, the genus Maytenus stands out for having the highest number of species, and one of these species is Maytenus guianensis, popularly known as chichuá, xixuá, chuchahuasi, chucchu huashu, chuchuasi, and chuchasha. It is a medium-sized tree typical of the Amazon rainforest with various therapeutic properties. Despite its prevalent use in traditional medicine, there is a gap in the phytochemical exploration of the species in the Amazon, especially in the Alto Solimões region. Thus, this study evaluated the current state of research related to the biological activities and identification of chemical compounds in M. guianensis in the northern region. For this purpose, articles were selected from the Google Scholar and Scielo databases, covering the period from 2007 to 2022, as well as dissertations and theses within the same timeframe. A total of 50 scientific works were consulted, including 20 dissertations, 10 theses, and 20 articles. The analysis of the studies revealed, in general, that the roots, bark, stems, and leaves of M. guianensis exhibit various biological properties, including analgesic, anti-inflammatory, antirheumatic, antidiarrheal, antioxidant, muscle relaxant, anticytotoxic, antimutagenic, antigyotoxic, antimicrobial, and antiparasitic actions. Regarding the isolated chemical compounds from the species, these occur in different parts of the plant, with the majority belonging to the terpene class, notably 3-oxo-friedelane triterpene, 29-hydroxyfriedelan-3-one triterpene, 16β-hydroxyfriedelan-3-one triterpene, tingenin B, and tingenone. Finally, the dissemination of this study is of utmost relevance as it encourages further research with medicinal plants, particularly focusing on M. guianensis. This effort will significantly contribute to the advancement of scientific knowledge about medicinal plants in the Alto Solimões Region.

Structure-Activity Relationship of a Pyrrole Based Series of PfPKG Inhibitors as Anti-Malarials.

Controlling malaria requires new drugs against Plasmodium falciparum. The P. falciparum cGMP-dependent protein kinase (PfPKG) is a validated target whose inhibitors could block multiple steps of the parasite's life cycle. We defined the structure-activity relationship (SAR) of a pyrrole series for PfPKG inhibition. Key pharmacophores were modified to enable full exploration of chemical diversity and to gain knowledge about an ideal core scaffold. In vitro potency against recombinant PfPKG and human PKG were used to determine compound selectivity for the parasite enzyme. P. berghei sporozoites and P. falciparum asexual blood stages were used to assay multistage antiparasitic activity. Cellular specificity of compounds was evaluated using transgenic parasites expressing PfPKG carrying a substituted "gatekeeper" residue. The structure of PfPKG bound to an inhibitor was solved, and modeling using this structure together with computational tools was utilized to understand SAR and establish a rational strategy for subsequent lead optimization.

High Target Homology Does Not Guarantee Inhibition: Aminothiazoles Emerge as Inhibitors of Plasmodium falciparum.

In this study, we identified three novel compound classes with potent activity against Plasmodium falciparum, the most dangerous human malarial parasite. Resistance of this pathogen to known drugs is increasing, and compounds with different modes of action are urgently needed. One promising drug target is the enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) of the methylerythritol 4-phosphate (MEP) pathway for which we have previously identified three active compound classes against Mycobacterium tuberculosis. The close structural similarities of the active sites of the DXPS enzymes of P. falciparum and M. tuberculosis prompted investigation of their antiparasitic action, all classes display good cell-based activity. Through structure-activity relationship studies, we increased their antimalarial potency and two classes also show good metabolic stability and low toxicity against human liver cells. The most active compound 1 inhibits the growth of blood-stage P. falciparum with an IC50 of 600 nM. The results from three different methods for target validation of compound 1 suggest no engagement of DXPS. All inhibitor classes are active against chloroquine-resistant strains, confirming a new mode of action that has to be further investigated.

Late-Stage Diversification of Pyrazoles as Antileishmanial Agents.

N-Pyrazolylcarboxamides and N-pyrazolylureas represent promising lead compounds for the development of novel antileishmanial drugs. Herein, we report the late-stage diversification of 3-bromopyrazoles 10 A/B and 14 A by Pd-catalyzed Sonogashira and Suzuki-Miyaura cross coupling reactions. The electron-withdrawing properties of the cyano moiety in 4-position of the pyrazole ring limited the acylation of the primary amino moiety in 5-position. A large set of pyrazoles bearing diverse aryl and alkynyl substituents in 3-position was prepared and the antileishmanial and antitrypanosomal activity was recorded. The urea 38 lacking the electron withdrawing cyano moiety in 4-position and containing the large 4-benzylpiperidinoo moiety exhibited a modest antileishmanial (IC50=19 μM) and antitrypanosomal activity (IC50=7.9 μM)). However, its considerable toxicity against the PMM and MRC-5 cells indicates low selectivity, i. e. a small gap between the desired antiparasitic activity and undesired cytotoxicity of <2- to 4-fold.

Novel Bidentate Amine Ligand and the Interplay between Pd(II) and Pt(II) Coordination and Biological Activity.

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI50 of 10.5 μM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 μM.

In vitro antitrypanosomal activity of synthesized nitrofurantoin-triazole hybrids against Trypanosoma species causing animal African trypanosomosis

Animal African trypanosomosis (AAT) is a disease caused by Trypanosoma brucei brucei, T. vivax, T. evansi and T. congolense which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the in vitro anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal trypanosomes and evaluated their cytotoxicity using Madin–Darby bovine kidney cells. The n-alkyl sub-series hybrids, 8 (IC50 0.09 ± 0.02 μM; SI 686.45) and 9 (IC50 0.07 ± 0.04 μM; SI 849.31) had the highest anti-trypanosomal activity against T. b. brucei. On the contrary, the nonyl 6 (IC50 0.12 ± 0.06 μM; SI 504.57) and nitrobenzyl 18 (IC50 0.11 ± 0.03 μM; SI 211.07) displayed the highest trypanocidal activity against T. evansi. The nonyl hybrid 6 (IC50 0.02 ± 0.01 μM; SI 6328.76) was also detected alongside the undecyl 8 (IC50 0.02 ± 0.01 μM; SI 3454.36) and 3-bromobenzyl 19 (IC50 0.02 ± 0.01 μM; SI 2360.41) as the most potent hybrids against T. congolense. These hybrids had weak toxicity effects on the mammalian cells and highly selective submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.

Exploring the antifilarial potential of an important medicinal plant Typhonium trilobatum (L. Schoot): Isolation, characterization, and structural elucidation of bioactive compounds against Brugia malayi

Ethnopharmacology relevanceThe plant Typhonium trilobatum has been utilized in traditional medicine for the treatment of many ailments, including parasitic infections. Recent examinations indicate that the bioactive substances from this plant may have antiparasitic activities against Brugia malayi, which have not been determined. PurposeThe parasitic nematodes Brugia malayi, Brugia timori, and Wuchereria bancrofti causing lymphatic filariasis, remain a significant challenge to global public health. Given the ongoing nature of this enduring menace, the current research endeavours to examine the efficacy of an important medicinal plant, Typhonium trilobatum. MethodsDifferent extracts of the T. trilobatum tubers were evaluated for their antiparasitic activity. The most prominent extract was subjected to Gas Chromatography Mass Spectrometry (GC-MS) and High Performance Liquid Chromatography (HPLC) followed by Column Chromatography for isolating bioactive molecules. The major compounds were isolated and characterized based on different spectroscopic techniques (FTIR, NMR and HRMS). Further, the antiparasitic activity of the isolated compounds was evaluated against B. malayi and compared with clinically used antifilarial drugs like Diethylcarbamazine and Ivermectin. ResultsThe methanolic extract of the tuber exhibited significant antiparasitic activity compared to the other extracts. The bioactive molecules isolated from the crude extract were identified as Linoleic acid and Palmitic acid. Antiparasitic activity of both the compounds has been performed against B. malayi and compared with clinically used antifilarial drugs, Ivermectin and DEC. The IC50 value of Linoleic acid was found to be 6.09 ± 0.78 μg/ml after 24 h and 4.27 ± 0.63 μg/ml after 48 h, whereas for Palmitic acid the value was 12.35 ± 1.09 μg/ml after 24 h and 8.79 ± 0.94 μg/ml after 48 h. The IC50 values of both the molecules were found to be similar to the standard drug Ivermectin (IC50 value of 11.88 ± 1.07 μg/ml in 24 h and 2.74 ± 0.43 μg/ml in 48 h), and much better compared to the DEC (IC50 values of 194.2 ± 2.28 μg/ml in 24 h and 101.8 ± 2.06 μg/ml in 48 h). Furthermore, it has been observed that both the crude extracts and the isolated compounds do not exhibit any detrimental effects on the J774.A.1 macrophage cell line. ConclusionThe isolation and characterization of bioactive compounds present in the methanolic tuber extract of Typhonium trilobatum were explored. Moreover, the antimicrofilarial activity of the crude extracts and its two major compounds were determined using Brugia malayi microfilarial parasites without any significant side effects.

Antifungal and Antiparasitic Activities of Metallocene-Containing Fluconazole Derivatives.

The search for new anti-infectives based on metal complexes is gaining momentum. Among the different options taken by researchers, the one involving the use of organometallic complexes is probably the most successful one with a compound, namely, ferroquine, already in clinical trials against malaria. In this study, we describe the preparation and in-depth characterization of 10 new (organometallic) derivatives of the approved antifungal drug fluconazole. Our rationale is that the sterol 14α-demethylase is an enzyme part of the ergosterol biosynthesis route in Trypanosoma and is similar to the one in pathogenic fungi. To demonstrate our postulate, docking experiments to assess the binding of our compounds with the enzyme were also performed. Our compounds were then tested on a range of fungal strains and parasitic organisms, including the protozoan parasite Trypanosoma cruzi (T. cruzi) responsible for Chagas disease, an endemic disease in Latin America that ranks among some of the most prevalent parasitic diseases worldwide. Of high interest, the two most potent compounds of the study on T. cruzi that contain a ferrocene or cobaltocenium were found to be harmless for an invertebrate animal model, namely, Caenorhabditis elegans (C. elegans), without affecting motility, viability, or development.

Multitarget anti-parasitic activities of isoquinoline alkaloids isolated from Hippeastrum aulicum (Amaryllidaceae)

BackgroundChagas disease and leishmaniasis affect a significant portion of the Latin American population and still lack efficient treatments. In this context, natural products emerge as promising compounds for developing more effective therapies, aiming to mitigate side effects and drug resistance. Notably, species from the Amaryllidaceae family emerge as potential reservoirs of antiparasitic agents due to the presence of diverse biologically active alkaloids. PurposeTo assess the anti-Trypanosoma cruzi and anti-Leishmania infantum activity of five isolated alkaloids from Hippeastrum aulicum Herb. (Amaryllidaceae) against different life stages of the parasites using in silico and in vitro assays. Furthermore, molecular docking was employed to evaluate the interaction of the most active alkaloids. MethodsFive natural isoquinoline alkaloids isolated in suitable quantities for in vitro testing underwent preliminary in silico analysis to predict their potential efficacy against Trypanosoma cruzi (amastigote and trypomastigote forms) and Leishmania infantum (amastigote and promastigote forms). The in vitro antiparasitic activity and mammalian cytotoxicity were investigated with a subsequent comparison of both analysis (in silico and in vitro) findings. Additionally, this study employed the molecular docking technique, utilizing cruzain (T. cruzi) and sterol 14α-demethylase (CYP51, L. infantum) as crucial biological targets for parasite survival, specifically focusing on compounds that exhibited promising activities against both parasites. ResultsThrough computational techniques, it was identified that the alkaloids haemanthamine (1) and lycorine (8) were the most active against T. cruzi (amastigote and trypomastigote) and L. infantum (amastigote and promastigote), while also revealing unprecedented activity of alkaloid 7‑methoxy-O-methyllycorenine (6). The in vitro analysis confirmed the in silico tests, in which compound 1 presented the best activities against the promastigote and amastigote forms of L. infantum with half-maximal inhibitory concentration (IC50) 0.6 µM and 1.78 µM, respectively. Compound 8 exhibited significant activity against the amastigote form of T. cruzi (IC50 7.70 µM), and compound 6 demonstrated activity against the trypomastigote forms of T. cruzi and amastigote of L. infantum, with IC50 values of 89.55 and 86.12 µM, respectively. Molecular docking analyses indicated that alkaloids 1 and 8 exhibited superior interaction energies compared to the inhibitors. ConclusionThe hitherto unreported potential of compound 6 against T. cruzi trypomastigotes and L. infantum amastigotes is now brought to the forefront. Furthermore, the acquired dataset signifies that the isolated alkaloids 1 and 8 from H. aulicum might serve as prototypes for subsequent structural refinements aimed at the exploration of novel leads against both T. cruzi and L. infantum parasites.

Potential Effects of Garlic (Allium sativum L.) on the Performance, Immunity, Gut Health, Anti-Oxidant Status, Blood Parameters, and Intestinal Microbiota of Poultry: An Updated Comprehensive Review

The use of antibiotics as growth promoters or for the prevention of some poultry diseases has faced global concern and serious criticism. Their addition to poultry feed has shown hazardous effects, including the development of antimicrobial resistance and a potentially harmful effect on human health. To eliminate these threats, there is increasing interest in natural alternatives. Plant derivatives such as garlic (Allium sativum L.) and its derivatives are presently extensively used in the poultry production system. The dietary supplementation of broilers and layers with garlic induced improvement in the production parameters, carcass quality, and intestinal integrity. The modulation of the immune response against some important viral diseases has resulted from the supplementation of poultry with garlic. Moreover, garlic has been shown to modulate gut health through antibacterial and antiparasitic activities. Treatment with garlic can also mitigate oxidative stress and reduce free-radical production. The reduction of cholesterol levels and improvement of some liver and blood parameters were also reported following the dietary inoculation of garlic. This review was designed to investigate the influence of garlic as a dietary additive on the performance, immunity, gut health, anti-oxidant status, blood parameters, and intestinal microbiota of poultry.

New myxobacteria of the Myxococcaceae clade produce angiolams with antiparasitic activities.

In the past century, microbial natural products have proven themselves to be substantial and fruitful sources of anti-infectives. In addition to the well-studied Actinobacteria, understudied bacterial taxa like the Gram-negative myxobacteria have increasingly gained attention in the ongoing search for novel and biologically active natural products. In the course of a regional sampling campaign to source novel myxobacteria, we recently uncovered new myxobacterial strains MCy12716 and MCy12733 belonging to the Myxococcaceae clade. Early bioactivity screens of the bacterial extracts revealed the presence of bioactive natural products that were identified as angiolam A and several novel derivatives. Sequencing of the corresponding producer strains allowed the identification of the angiolam biosynthetic gene cluster, which was verified by targeted gene inactivation. Based on bioinformatic analysis of the biosynthetic gene cluster, a concise biosynthesis model was devised to explain angiolam biosynthesis. Importantly, novel angiolam derivatives uncovered in this study named angiolams B, C, and D were found to display promising antiparasitic activities against the malaria pathogen Plasmodium falciparum in the 0.3-0.8 µM range.IMPORTANCEThe COVID-19 pandemic and continuously emerging antimicrobial resistance (AMR) have recently raised awareness about limited treatment options against infectious diseases. However, the shortage of treatment options against protozoal parasitic infections, like malaria, is much more severe, especially for the treatment of so-called neglected tropical diseases. The detection of anti-parasitic bioactivities of angiolams produced by MCy12716 and MCy12733 displays the hidden potential of scarcely studied natural products to have promising biological activities in understudied indications. Furthermore, the improved biological activities of novel angiolam derivatives against Plasmodium falciparum and the evaluation of its biosynthesis display the opportunities of the angiolam scaffold on route to treat protozoal parasitic infections as well as possible ways to increase the production of derivatives with improved bioactivities.