Antileishmanial Activity Research Articles

Antileishmanial Activity, Toxicity and Mechanism of Action of Complexes of Sodium Usnate with Lanthanide Ions: Eu(III), Sm(III), Gd(III), Nd(III), La(III) and Tb(III).

Leishmaniases are neglected diseases with limited therapeutic options. Diffuse cutaneous leishmaniasis can occur in Brazil due to Leishmania amazonensis. This study details the antileishmanial activity and cytotoxicity of complexes of sodium usnate (SAU) with lanthanide ions ([LnL3 (H2O)x] (Ln = La(III), Nd(III), Gd(III), Tb(III), Eu(III) and Sm(III); L = SAU). All lanthanide complexes were highly active and more potent than SAU against L. amazonensis promastigotes and intracellular amastigotes (Pro: IC50 < 1.50 μM; Ama: IC50 < 7.52 μM). EuL3·3H2O and NdL3·3H2O were the most selective and effective on intracellular amastigotes, with a selectivity index of approximately 7.0. In silico predictions showed no evidence of mutagenicity, tumorigenicity or irritation for all complexes. Treatment with EuL3·3H2O triggered NO release even at the lowest concentration, indicating NO production as a mechanism of action against the parasite. Incubating promastigotes with the lanthanide complexes, particularly with SmL3·4H2O and GdL3·3H2O, led to a change in the mitochondrial membrane potential, indicating the ability of these complexes to target this essential organelle. The same complexes caused cell death through cell membrane disruption, but their relationship with early or late apoptotic processes remains unclear. Thus, the inclusion of lanthanide ions in SAU improves selectivity with a promising mechanism of action targeting the mitochondria.

Amphotericin B loaded nanoemulsion: Optimization, characterization and in-vitro activity against L. donovani promastigotes

The present work aimed to develop and evaluate AmB-loaded nano-emulsion (AmB-NE) which will augment the solubility of AmB and lead to enhanced anti-leishmanial activity. The composition of AmB-NE was optimized by systematic screening followed by DoE-extreme vertices mixture design. The optimized NE revealed mean droplet size and PDI of 44.19 ± 5.5 nm, 0.265 ± 0.0723, respectively. The NE could efficiently encapsulate AmB with drug content and efficiency 83.509 ± 0.369% and 81.659 ± 0.013%, respectively. The presence of cholesterol and stearyl amine retarded the release (P < 0.0001) of AmB significantly compared to AmB suspension. The AmB-NE and pure AmB suspension demonstrated the IC50 of 0.06309 μg/mL and 0.3309 μg/mL against L.donovani promastigotes after 48 h incubation. The formulation was robust at all exaggerated stability conditions such as freeze-thaw and centrifugation. These findings indicate that AmB-NE is an attractive approach to treat visceral leishmaniasis with improved activity.

Evidence of Guanidines Potential against Leishmania (Viannia) braziliensis: Exploring In Vitro Effectiveness, Toxicities and of Innate Immunity Response Effects.

Leishmaniasis is a complex group of infectious and parasitic diseases that afflict many thousands of individuals across five continents. Leishmaniasis treatment remains a challenge because it relies on drugsknown for their high toxicity and limited efficacy, making itimperative to identify new molecules that offer greater effectiveness and safety. This study sought to explore the impact of seven synthetic guanidine derivatives (LQOF-G1, LQOF-G2, LQOF-G6, LQOF-G7, LQOF-G32, LQOF-G35 and LQOF-G36) onthe parasite Leishmania (Viannia) braziliensis and in vitro macrophage infection by this parasite, as well as cytotoxic approaches in vitro models of mammalian host cells and tissues. The synthesized compounds showed purity ≥ 99.65% and effectively inhibited parasite growth. LQOF-G1 proved the most potent, yielding the best half-maximal inhibitory concentration (IC50) values against promastigotes (4.62 μmol/L), axenic amastigotes (4.27 μmol/L), and intracellular amastigotes (3.65 μmol/L). Notably, the antileishmanial activity of LQOF-G1, LQOF-G2, and LQOF-G6 was related to immunomodulatory effects, evidenced by alterations in TNF-α, IL-12, IL-10, nitric oxide (NO), and reactive oxygen species (ROS) levels in the supernatant of culture macrophages infected with L. (V.) braziliensis and coincubated with these compounds. LQOF-G2 and LQOF-G36 compounds exhibited vasodilator and spasmolytic effects at higher concentrations (≥100 μmol/L). Generally, LQOF-G1, LQOF-G2, and LQOF-G32 compounds were found to be nontoxic to assessed organs and cells. No toxic effects were observed in human cell lines, such as HEK-293, CaCo-2 and A549, at concentrations ≥ 500 μmol/L. Collectively, data have shown unequivocal evidence of the effectiveness of these compounds against L. (V.) braziliensis parasite, one of the causative agents of Tegumentary Leishmaniasis and Mucocutaneous Leishmaniasis in America.

Leishmanicidal Activity of Moringa oleifera (L.) Leaf Protein Extract on the Indian Strain of Leishmania donovani: An In Vitro Study

IntroductionRecurring incidents of drug resistance and the health hazards associated with the chemotherapeutic treatment of visceral leishmaniasis necessitate the search for safer yet equally effective biologically available alternate therapeutics. Plant products are being emphasised in this regard. Thus, Moringa oleifera leaf was chosen here, and an in vitro study was undertaken to determine its antileishmanial activity against visceral leishmaniasis. MethodsThe protein in M. oleifera leaf extract (Mo-EX) was identified by denaturing polyacrylamide gel electrophoresis. The antipromastigote activity and cytotoxicity of the proteinaceous Mo-EX were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Phase contrast microscopy and scanning electron microscopy analyses confirmed the morphological alterations of the promastigotes. The anti-amastigote activity of Mo-EX was determined by microscopic intracellular counting. Apoptosis, reactive oxygen species (ROS) generation, and thiol depletion were assessed by flow cytometric analysis, and nitric oxide production was determined by colorimetric assays. ResultsM. oleifera leaf extract displayed 50% inhibitory concentration valuesagainst Leishmania donovani promastigotes and intracellular amastigotes of 11.85 ± 0.08 and 8.86 ± 0.03 μg/ml, respectively, with a 50% lethal concentration in RAW 264.7 macrophages of 2 036.25 ± 0.04 μg/ml. Mo-EX reduced thiol production, significantly increased ROS generation, and induced apoptosis in L. donovani promastigotes while altering their morphology. Mo-EX evoked ROS and nitric oxide generation in parasite-infected host cells ex vivo. ConclusionsThe findings of the present study elucidate the leishmanicidal activity of protein-rich Mo-EX in L. donovani (MHOM/IN/1983/AG83) promastigotes and amastigotes, and Mo-EX was found to be moderately safe in RAW 264.7 host macrophages in vitro.

Leishmanicidal activity and 4Dquantitative structure-activity relationship and molecular docking studies of vanillin-containing 1,2,3-triazole derivatives.

Aim: The assessment of the antileishmanial potential of 22 vanillin-containing 1,2,3-triazole derivatives against Leishmania braziliensis is reported. Materials & methods: Initial screening was performed against the parasite promastigote form. The most active compound, 4b, targeted parasites within amastigotes (IC50=4.2±1.0μmol l-1), presenting low cytotoxicity and a selective index value of 39. 4D quantitative structure-activity relationship and molecular docking studies provided insights into structure-activity and biological effects. Conclusion: A vanillin derivative with significant antileishmanial activity was identified. Enhanced activity was linked to increased electrostatic and Van der Waals interactions near the benzyl ring of the derivatives. Molecular docking indicated the inhibition of the Leishmania amazonensis sterol 14α-demethylase, using Leishmania infantum sterol 14α-demethylase as a model, without affecting the human isoform. Inhibition was active site competition with lanosterol.

In vitro antileishmanial activity of thioridazine on amphotericin B unresponsive/ sensitive Leishmania donovani promastigotes and intracellular amastigotes

The recent increase in the drug (liposomal amphotericin-B) unresponsive cases becomes hostile for the visceral leishmaniasis (VL) elimination target. The quest for new antileishmanial drugs is on the way and may demand more time. Meanwhile, drug repurposing is a quite promising option to explore further. We made such an attempt with thioridazine (TRZ), a first-line antipsychotic drug, which was reported for antimicrobial activity. In this study, we evaluated the drug activity of TRZ against amphotericin-B (Amp-B) sensitive and unresponsive Leishmania donovani promastigotes, as well as intracellular amastigotes (drug sensitive). We observed a potent antileishmanial activity of TRZ with significantly low half maximal inhibitory concentrations (IC50) on both the variants of promastigotes (0.61 ± 0.15 μM). These concentrations are comparable to the previously reported IC50 concentration of the current antileishmanial drug (Amp-B) against L. donovani. Light microscopy reveals the perturbations in promastigote morphology upon TRZ treatment. The in vitro studies on human macrophage cell lines determine the 50% cytotoxicity concentration (CC50) of TRZ on host cells as 20.046 μM and a half maximal effective concentration (EC50) as 0.91 μM during L. donovani infection, in turn selectivity index (SI) was calculated as 22.03 μM. Altogether, the results demonstrate that TRZ has the potential for drug repurposing and further studies on animal models could provide better insights for VL treatment.

Correlation between secondary metabolites of Iris confusa Sealy and Iris pseudacorus L. and their newly explored antiprotozoal potentials

BackgroundIn the last few decades, the use of plant extracts and their phytochemicals as candidates for the management of parasitic diseases has increased tremendously. Irises are aromatic and medicinal plants that have long been employed in the treatment of different infectious diseases by traditional healers in many cultures. This study aims to explore the potential of three common Iris species (I. confusa Sealy, I. pseudacorus L. and I. germanica L.) against infectious diseases. Their in vitro antiprotozoal potency against Plasmodium falciparum, Trypanosoma brucei brucei, T. b. rhodesiense, T. cruzi and Leishmania infantum beside their cytotoxicity on MRC-5 fibroblasts and primary peritoneal murine macrophages were examined.MethodsThe secondary metabolites of the tested extracts were characterized by UPLC-HRMS/MS and Pearsons correlation was used to correlate them with the antiprotozoal activity.ResultsOverall, the non-polar fractions (NPF) showed a significant antiprotozoal activity (score: sc 2 to 5) in contrast to the polar fractions (PF). I. confusa NPF was the most active extract against P. falciparum [IC50 of 1.08 μg/mL, selectivity index (S.I. 26.11) and sc 5] and L. infantum (IC50 of 12.7 μg/mL, S.I. 2.22 and sc 2). I. pseudacorus NPF was the most potent fraction against T. b. rhodesiense (IC50 of 8.17 μg/mL, S.I. 3.67 and sc 3). Monogalactosyldiacylglycerol glycolipid (18:3/18:3), triaceylglycerol (18:2/18:2/18:3), oleic acid, and triterpenoid irridals (spirioiridoconfal C and iso-iridobelamal A) were the top positively correlated metabolites with antiplasmodium and antileishmanial activities of I. confusa NPF. Tumulosic acid, ceramide sphingolipids, corosolic, maslinic, moreollic acids, pheophytin a, triaceylglycerols, mono- and digalactosyldiacylglycerols, phosphatidylglycerol (22:6/18:3), phosphatidylcholines (18:1/18:2), and triterpenoid irridal iso-iridobelamal A, were highly correlated to I. pseudacorus NPF anti- T. b. rhodesiense activity. The ADME study revealed proper drug likeness properties for certain highly corelated secondary metabolites.ConclusionThis study is the sole map correlating I. confusa and I. pseudacorus secondary metabolites to their newly explored antiprotozoal activity.

Synthesis, Antimalarial, Antileishmanial, and Cytotoxicity Activities and Preliminary In Silico ADMET Studies of 2-(7-Chloroquinolin-4-ylamino)ethyl Benzoate Derivatives.

A series of heterocyclic chloroquine hybrids, containing a chain of two carbon atoms at position four of the quinolinic chain and acting as a link between quinoline and several benzoyl groups, is synthesized and screened in vitro as an inhibitor of β-hematin formation and in vivo for its antimalarial activity against chloroquine-sensitive strains of Plasmodium berghei ANKA in this study. The compounds significantly reduced haeme crystallization, with IC50 values < 10 µM. The values were comparable to chloroquine's, with an IC50 of 1.50 ± 0.01 µM. The compounds 4c and 4e prolonged the average survival time of the infected mice to 16.7 ± 2.16 and 14.4 ± 1.20 days, respectively. We also studied the effect of the compounds 4b, 4c, and 4e on another important human parasite, Leishmania mexicana, which is responsible for cutaneous leishmaniasis, demonstrating a potential leishmanicidal effect against promasigotes, with an IC50 < 10 µM. Concerning the possible mechanism of action of these compounds on Lesihmania mexicana, we performed experiments demonstrating that these three compounds could induce the collapse of the parasite mitochondrial electrochemical membrane potential (Δφ). The in vitro cytotoxicity assays against mammalian cancerous and noncancerous human cell lines showed that the studied compounds exhibit low cytotoxic effects. The ADME/Tox analysis predicted moderate lipophilicity values, low unbound fraction values, and a poor distribution for these compounds. Therefore, moderate bioavailability was expected. We calculated other molecular descriptors, such as the topological polar surface area, according to Veber's rules, and except for 2 and 4i, the rest of the compounds violated this descriptor, demonstrating the low antimalarial activity of our compounds in vivo.

In Vitro and In Vivo Antileishmanial Activity of Thioridazine

IntroductionLeishmaniasis is a neglected disease with high prevalence and incidence in tropical and subtropical areas. Existing drugs are limited due to cost, toxicity, declining efficacy and unavailability in endemic places. Drug repurposing has established as an efficient way for the discovery of drugs for a variety of diseases.PurposeThe objective of the present work was testing the antileishmanial activity of thioridazine, an antipsychotic agent with demonstrated effect against other intracellular pathogens.MethodsThe cytotoxicity for mouse peritoneal macrophages as well as the activity against Leishmania amazonensis, Leishmania mexicana and Leishmania major promastigotes and intracellular amastigotes, as well as in a mouse model of cutaneous leishmaniasis, were assessed.ResultsThioridazine inhibited the in vitro proliferation of promastigotes (50% inhibitory concentration—IC50—values in the range of 0.73 µM to 3.8 µM against L. amazonensis, L. mexicana and L. major) and intracellular amastigotes (IC50 values of 1.27 µM to 4.4 µM for the same species). In contrast, in mouse peritoneal macrophages, the 50% cytotoxic concentration was 24.0 ± 1.89 µM. Thioridazine inhibited the growth of cutaneous lesions and reduced the number of parasites in the infected tissue of mice. The dose of thioridazine that inhibited lesion development by 50% compared to controls was 23.3 ± 3.1 mg/kg and in terms of parasite load, it was 11.1 ± 0.97 mg/kg.ConclusionsThioridazine was effective against the promastigote and intracellular amastigote stages of three Leishmania species and in a mouse model of cutaneous leishmaniasis, supporting the potential repurposing of this drug as an antileishmanial agent.

HPLC method for quantifying verbascoside in Stizophyllum perforatum and assessment of verbascoside acute toxicity and antileishmanial activity.

We report the chemical composition of the crude leaf extracts obtained from Stizophyllum perforatum (Cham.) Miers (Bignoniaceae), a simple high-performance liquid chromatography-diode array detection (HPLC-DAD) method based on mangiferin as an internal standard to quantify verbascoside, and the verbascoside acute oral toxicity and antileishmanial activity. HPLC-high-resolution mass spectrometry-DAD (HPLC-HRMS-DAD) analyses of the crude ethanol S. perforatum leaf extracts (CE-1 and CE-2) revealed that verbascoside was the major constituent in both extracts. CE-1 was purified, and verbascoside and casticin, among other compounds, were isolated. The developed HPLC-DAD method was validated and met the required standards. Investigation of the CE-2 acute toxicity indicated a lethal dose (LD50) greater than 2,000 mg/kg of body weight. Both CE-1 and CE-2 exhibited antileishmanial activity. The isolated compounds, verbascoside and casticin, also displayed antileishmanial activity with effective concentrations (IC50) of 6.23 and 24.20 µM against promastigote forms and 3.71 and 18.97 µM against amastigote forms of Leishmania amazonensis, respectively, but they were not cytotoxic to J774A.1 macrophages. Scanning electron microscopy of the L. amazonensis promastigotes showed that the parasites became more rounded and that their plasma membrane was altered in the presence of verbascoside. Additionally, transmission electron microscopy demonstrated that vacuoles emerged, lipids accumulated, kinetoplast size increased, and interstitial extravasation occurred in L. amazonensis promastigotes exposed to verbascoside. These findings suggest that S. perforatum is a promising candidate for further in vivo investigations against L. amazonensis.

Synthesis and evaluation of hybrid sulfonamide-chalcones with potential antileishmanial activity.

Leishmaniasis is an emerging tropical infectious disease caused by a protozoan parasite of the genus Leishmania. In this work, the molecular hybridization between a trimethoxy chalcone and a sulfonamide group was used to generate a series of sulfonamide-chalcones. A series of eight sulfonamide-chalcone hybrids were made with good yields (up to 95%). These sulfonamide-chalcones were tested against promastigotes of Leishmania amazonensis and cytotoxicity against mouse macrophages, which showed good antileishmanial activity with IC50 = 1.72-3.19 µM. Three of them (10c, 10g, and 10h) were also highly active against intracellular amastigotes and had a good selectivity index (SI > 9). Thus, those three compounds were docked in the cytosolic tryparedoxin peroxidase (cTXNPx) enzyme of the parasite, and molecular dynamics simulations were carried out. This enzyme was selected as a target protein for the sulfonamide-chalcones due to the fact of the anterior report, which identified a strong and stable interaction between the chalcone NAT22 (6) and the cTXNPx. In addition, a prediction of the drug-likeness, and the pharmacokinetic profile of all compounds were made, demonstrating a good profile of those chalcones.

In Vitro Activity of Green Synthesized Silver Nanoparticles via Thymus Vulgaris Extract against Leishmania major.

We aimed to assess the in vitro effects of the green synthesized silver nanoparticles (Ag NPs) via Thymus vulgaris (thyme) against Leishmania major infection. We have prepared T. vulgalis silver nanoparticles (TSNPs) by adding thyme extract to the silver nitrate aqueous solution (0.2 mM), and evaluated their antileishmanial activity. The viability of L. major promastigotes was assessed in the presence of various concentrations of TSNPs by direct counting after 24 h. The MTT assay was used to identify the viability of promastigotes. The same procedures were assessed in uninfected macrophage cells. The apoptotic effects of nanoparticles on L. major promastigotes were determined by flow cytometry assay using annexin staining. To evaluate anti-amastigotes activity of TSNPs, light microscopic observation was used to determine the number of parasites within the macrophages in each well. The effect of TSNPs on promastigotes and amastigotes of L. major was effective and had a reverse relationship with its concentration. TSNPs, inhibited the growth rate of L. major amastigotes and, the IC50 value of these nanoparticles was estimated 3.02 μg/mL (28 μM) after 72h. The results of flow cytometry showed that the toxic effects of TSNPs on promastigotes after 24 hours were statistically significant (P<0.05) and showed 69.51% of apoptosis. TSNPs had an inhibitor effect on promastigote and amastigote forms of L. major in vitro. It might be considered as a candidate for the treatment of this infection.

Green Synthesis, Characterization, and Antileishmanial Activity of the Silver Nanoparticles Alone and Along with Meglumine Antimoniate against Leishmania major Infection.

The most commonly available drugs for leishmaniasis are pentavalent antimony compounds; whereas the recent studies showed various complications and limitations of these drugs. We aimed to green synthesized silver nanoparticles (AgNPs) and study the promising antileishmanial and synergic effects of green synthesized silver nanoparticles alone and combined with glucantime. The precipitation technique was used to drop silver ions via an extract of Astragalus spinosus to AgNPs at Department of Biological Sciences, Faculty of Science and Humanities, Shaqra University, Saudi Arabia in 2022. Then, its anti-amastigotes, caspase-3-like activity, triggering the nitric oxide (NO) as well as its cytotoxicity effects on macrophage cells as well as effects on leishmaniasis in BALB/c mice infected by L. major were measured. The size of the AgNPs were ranging from 30-40 nm. The IC50 value for AgNPs, AgNPs+ meglumine antimoniate (MA), and MA was 59.3, 18.6, and 51.2 μg/mL, respectively. The determined FIC value for AgNPs and MA was found to be 0.31 and 0.36, respectively; demonstrating the synergistic potency of AgNPs when combined with MA. The diameter of CL lesions treated with various doses of AgNPs and AgNPs+MA notably (p<0.001) decreased. AgNPs, particularly at the concentrations of ½ IC50 and IC50, considerably triggered the caspase-3 activation. The calculated CC50 of AgNPs and MA was 612.5 and 789.8 μg/mL, respectively. Green synthesized AgNPs, especially in combination with MA had synergic antileishmanial effects and displayed a promising drug candidate for treating L. major CL. We found satisfactory findings in the parasite reduction in both in vitro and animal models. Still, more studies are expected to explain the precise action mechanisms of AgNPs and their efficacy in humans.

Amphotericin B-Loaded Extracellular Vesicles Derived from Leishmania major Enhancing Cutaneous Leishmaniasis Treatment through In Vitro and In Vivo Studies.

Recent studies have shown an increasing number of patients with cutaneous leishmaniasis (CL) who do not respond to pentavalent antimonials as the first line of treatment for CL. Nanocarriers such as extracellular vesicles (EVs) are efficient vehicles that might be used as drug delivery systems for the treatment of diseases. Therefore, we aimed to isolate and characterize the EVs of Leishmania major, load them with Amphotericin B (AmB), and investigate the toxicity and efficacy of the prepared drug form. The EVs of L. major were isolated, characterized, and loaded with amphotericin B (AmB), and the EVs-Amphotericin B (EVs-AmB) form was synthesized. Relevant in vitro and in vivo methods were performed to evaluate the toxicity and efficacy of EVs-AmB compared to the control. The anti-leishmanial activity of the EVs-AmB showed a higher percentage inhibition (PI%) (P = 0.023) compared to the AmB at different concentrations and time points. Obtained data showed a significant increase in the lesion size and parasite load in the lesion, PBS, and EVs mice groups in comparison with EVs-AmB, AmB, and Glucantime groups (P < 0.05), EVs-AmB had a significant decrease in lesion sizes in comparison with AmB (P < 0.05). Results showed that EVs-AmB decreased its toxicity to the kidneys and liver (P < 0.05). EVs-AmB improved the efficacy of AmB in mouse skin lesions and reduced hepatorenal toxicity. Furthermore, EVs could be a promising nanoplatform for the delivery of AmB in CL caused by L. major.

Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents.

Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (1-25) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites.

Green Synthesis and Characterization of Silver Nanoparticles from Eclipta alba and Its Activity Against Triple-Negative Breast Cancer Cell Line (MDA-MB-231).

Triple-negative breast cancer (TNBC) doesn't have well-defined molecular targets making it unable to treat with chemotherapy also have faster metastatic rate and worse survival rate. In the current study we aim to target TNBC through eco-friendly green synthesized silver nanoparticles having anti-cancer phytoconstituents from the traditional anti-cancer medicinal plant Eclipta alba. Green synthesized silver nanoparticles (AgNPs) are agglomerates of spherical shaped 40-60nm sized showing characteristic light absorption at 437nm, banding pattern at 1479, 1285, 1036, and 471 showing and further X-ray diffraction pattern confirm face-centered cubic crystal silver structure exist in the green synthesized silver nanoparticle preparation. Further in vitro anti-oxidant analysis results revealed that green synthesized AgNPs showed 2.6-fold higher anti-oxidant potential (IC50 15.70g/ml) than that of aqueous plant leaf extract (IC50 39.80g/ml). In MTT cytotoxicity analysis Eclipta alba plant extract and AgNPs both display dose-dependent cytotoxicity against triple-negative breast cancer cells (MDA-MB-231), although their IC50 values differ substantially, at 105.80µg/ml and 77.20g/ml, respectively. Finally, AgNPs from Eclipta alba tested for anti-leishmanial activity and it showed 91.36 ± 1.05 for promastigotes and 76.62 ± 0.95 for amastigotes at the highest dose of 400g/ml. Altogether present data showed that Eclipta alba leaf extract actively bonded with silver nanoparticles suppresses the MDA-MB-231 cells growth through high antioxidant characters and anti-leishmanial activity. From together we confirm that Eclipta alba was recommended to a future therapeutic drug and agent to control breast cancer in the clinical level.

Phytochemical, cytotoxic, antileishmania and antimicrobial potentials of Rhodes grass (Chloris gayana Kunth)

The present study aimed to analyze the cytotoxic and antimicrobial activity of the plant Chloris gayana Kunth (Poaceae) proceeding from the ethanol extract, taking into consideration its major secondary metabolites, such as alkaloids, triterpenes, steroids, flavonoids, and tannins. The ethanol extract showed no antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida krusei. However, the ethanol extract was able to potentiate the activity of amikacin against a strain of S. aureus MRSA (methicillin resistant S. aureus), suggesting a possible application of the extract itself or its isolated phytochemicals, as adjuvants of amikacin in the treatment of infections caused by MRSA strains resistant to this antibiotic. Potential antileishmanial activity was observed, but further research on the isolated action of these metabolites is needed.

Synergistic antileishmanial activity of erythrodiol, uvaol, and oleanolic acid isolated from olive leaves of cv. Chemlali

Synergistic antileishmanial activity of erythrodiol, uvaol, and oleanolic acid isolated from olive leaves of cv. Chemlali

In Vitro and In Silico Evaluations of the Antileishmanial Activities of New Benzimidazole-Triazole Derivatives.

Benzimidazole and triazole rings are important pharmacophores, known to exhibit various pharmacological activities in drug discovery. In this study, it was purposed to synthesize new benzimidazole-triazole derivatives and evaluate their antileishmanial activities. The targeted compounds (5a-5h) were obtained after five chemical reaction steps. The structures of the compounds were confirmed by spectral data. The possible in vitro antileishmanial activities of the synthesized compounds were evaluated against the Leishmania tropica strain. Further, molecular docking and dynamics were performed to identify the probable mechanism of activity of the test compounds. The findings revealed that compounds 5a, 5d, 5e, 5f, and 5h inhibited the growth of Leishmania tropica to various extents and had significant anti-leishmanial activities, even if some orders were higher than the reference drug Amphotericin B. On the other hand, compounds 5b, 5c, and 5g were found to be ineffective. Additionally, the results of in silico studies have presented the existence of some interactions between the compounds and the active site of sterol 14-alpha-demethylase, a biosynthetic enzyme that plays a critical role in the growth of the parasite. Therefore, it can be suggested that if the results obtained from this study are confirmed with in vivo findings, it may be possible to obtain some new anti-leishmanial drug candidates.

An in vitro study of the antileishmanial and cytotoxic activity of extracts of Sclerolobium paniculatum (Fabaceae)

Leishmaniasis is a neglected endemic disease and the pharmacotherapy indicated is expensive, in addition to the unwanted effects generated by the drugs, resulting in low adherence to treatment. Therefore, the search for therapeutic alternatives includes the use of medicinal plants, such as Sclerolobium paniculatum Vogel, which has antioxidant, healing and antifungal properties. Therefore, the aim of this study was to evaluate the in vitro antileishmanial activity of the methanolic and hexanic extracts of S. paniculatum against the promastigote forms of Leishmania (L.) amazonensis and Leishmania (V.) guyanensis and their toxicity in J774 macrophages. As a result, the hexanic extract was considered active against L. guyanensis with an IC50 of 40 μg mL-1 over 48 hours, with no significant activity for L. amazonensis with an IC50 above 100 μg mL-1 over 24 and 48 hours. The methanolic extract showed moderate activity against L. guyanensis, with an IC50 of 82 μg mL-1 over 48 hours and an IC50 of 67 μg mL-1 over 48 hours against L. amazonensis, making it moderately active. Both extracts did not present cytotoxic profiles at any of the concentrations, being recommended for future research with other species of Leishmania sp. to optimize the treatment of cutaneous leishmaniasis.