Significant Antileishmanial Activity Research Articles

In vitro antileishmanial activities of hydro-methanolic crude extracts and solvent fractions of Clematis simensis fresen leaf, and Euphorbia abyssinica latex.

As a result of increasing drug resistance, crossover resistance development, prolonged therapy, and the absence of different agents with innovative methods for implementation, the efficacy of recent antileishmanial medications is severely declining. So, it is vital to look for other medications from botanical remedies that have antileishmanial activity. The latex of Euphorbia abyssinica (E abyssinica) and the leaves of Clematis simensis fresen (C simensis) were macerated in methanol (80%). In vitro antileishmanial activity of the preparation was tried on promastigotes of Leishmania aethiopica (L aethiopica) and Leishmania donovani (L donovani) using resazurin assay, and fluorescence intensity was measured. One percent of dimethyl sulfoxide (DMSO) and media as negative control and amphotericin B as positive control were used. Additionally, hemolytic & phytochemical tests of the preparation were done. The mean and standard errors of each extract were evaluated and interpreted for statistical significance using one-way analysis of variance. From sigmoidal dose-response curves of % inhibition, half maximal inhibitory concentration (IC50) values were determined by GraphPad Prism and Microsoft Excel; outcomes were presented as mean ± standard error of mean of triplicate trials. P < .05 was statistical significance. The phytochemical screening of C simensis and E abyssinica confirmed the existence of steroids, phenols, tannins, saponins, alkaloids, terpenoids, flavonoids and glycosides. C simensis possesses antileishmanial activity with IC50 outcomes of 46.12 ± 0.03 and 8.18 ± 0.10 µg/mL on the promastigotes of L aethiopica and L donovani, respectively. However, E abyssinica showed stronger activity with IC50 outcomes of 16.07 ± 0.05 µg/mL and 4.82 ± 0.07 µg/mL on L aethiopica and L donovani, respectively. C simensis and E abyssinica have a less hemolytic effect on human red blood cells at low concentrations. The outcomes from this investigation demonstrated that the preparation of C simensis and E abyssinica indicated significant antileishmanial activity. Therefore, further in vivo assessment of antileishmanial, cytotoxicity activity and quantitative identification of secondary metabolites are highly recommended.

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 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.

Design, synthesis, in vitro – In vivo biological evaluation of novel thiazolopyrimidine compounds as antileishmanial agent with PTR1 inhibition

The leishmaniasis are a group of vector-borne diseases caused by a protozoan parasite from the genus Leishmania. In this study, a series of thiazolopyrimidine derivatives were designed and synthesized as novel antileishmanial agents with LmPTR1 inhibitory activity. The final compounds were evaluated for their in vitro antipromastigote activity, LmPTR1 and hDHFR enzyme inhibitory activities, and cytotoxicity on RAW264.7 and L929 cell lines. Based on the bioactivity results, three compounds, namely L24f, L24h and L25c, were selected for evaluation of their in vivo efficacy on CL and VL models in BALB/c mice. Among them, two promising compounds, L24h and L25c, showed in vitro antipromastigote activity against L. tropica with the IC50 values of 0.04 μg/ml and 6.68 μg/ml; against L. infantum with the IC50 values of 0.042 μg/ml and 6.77 μg/ml, respectively. Moreover, the title compounds were found to have low in vitro cytotoxicity on L929 and RAW264.7 cell lines with the IC50 14.08 μg/ml and 21.03 μg/ml, and IC50 15.02 μg/ml and 8.75 μg/ml, respectively. LmPTR1 enzyme inhibitory activity of these compounds was determined as 257.40 μg/ml and 59.12 μg/ml and their selectivity index (SI) over hDHFR was reported as 42.62 and 7.02, respectively. In vivo studies presented that L24h and L25c have a significant antileishmanial activity against footpad lesion development of CL and at weight measurement of VL group in comparison to the reference compound, Glucantime®. Also, docking studies were carried out with selected compounds and other potential Leishmania targets to detect the putative targets of the title compounds. Taken together, all these findings provide an important novel lead structure for the antileishmanial drug development.

Holanamine, a Steroidal Alkaloid from the Bark of Holarrhena pubescens Wall. ex G. Don Inhibits the Growth of Leishmania donovani by Targeting DNA Topoisomerase 1B.

Leishmaniasis is a group of neglected tropical diseases (NTDs) caused by about 20 species of obligate intracellular protozoan parasites of the genus Leishmania, which occurs in cutaneous, mucocutaneous, and visceral forms. Many researchers have sought to utilize natural products for novel and effective treatments to combat many infectious diseases, including leishmaniasis. Holarrhena pubescens Wall. ex G. Don (Apocynaceae) bark is a rich source of bioactive steroidal alkaloids. The total alkaloidal extract (IC50 6.12 ± 0.117 μg/mL), and the isolated alkaloid, holanamine, showed significant antileishmanial activity (IC50 2.66 ± 0.112 μM against AG83 and 3.80 ± 0.126 μM against BHU-575) against the Leishmania donovani parasite, better than miltefosine (IC50 19.61 ± 0.093 μM against AG83 and 23.20 ± 0.094 μM against BHU-575). Holanamine inhibited the L. donovani topoisomerase 1B (LdToP1B) in a non-competitive manner (IC50 2.81 ± 0.105 μM), indicating that it interacts with the free enzyme and enzyme-DNA complex without inhibiting human topoisomerase. Hydrogen bonding and hydrophobic interactions of holanamine with the N-terminal and hinge region of the large subunit of LTop1B is responsible for its potent antileishmanial activity, as shown by docking studies. Treatment with holanamine causes apoptotic-like cell death by generating cellular and mitochondrial reactive oxygen species, disrupting the mitochondrial membrane potential and inducing ultrastructural alterations in the promastigotes. Holanamine effectively clears intracellular amastigotes but minimally affects host macrophages with no significant cytotoxicity in HEK 293 and L929 cell lines. Thus, our studies show that holanamine can further be used to develop effective antileishmanial agents against evolving drug-resistant parasites.

Synthesis of new 3-acetyl-1,3,4-oxadiazolines combined with pyrimidines as antileishmanial and antiviral agents.

A new series of 3-acetyl-1,3,4-oxadiazoline hybrid molecules was designed and synthesized using a condensation between acyclonucleosides and substituted phenylhydrazone. All intermediates and final products were screened against Leishmania donovani, a Protozoan parasite and against three viruses SARS-CoV-2, HCMV and VZV. While no significant activity was observed against the viruses, the intermediate with 6-azatymine as thymine and 5-azathymine-3-acetyl-1,3,4-oxadiazoline hybrid exhibited a significant antileishmanial activity. The later compound was the most promising, exhibiting an IC50 value at 8.98 µM on L. donovani intramacrophage amastigotes and a moderate selectivity index value at 2.4.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s11030-022-10548-9.

Eugenol derivatives with 1,2,3-triazole moieties: Oral treatment of cutaneous leishmaniasis and a quantitative structure-activity relationship model for their leishmanicidal activity

Leishmaniasis is a group of neglected vector-borne tropical diseases caused by protozoan parasites of the genus Leishmania that multiply within phagocytic cells and have a wide range of clinical manifestations. Cutaneous leishmaniasis (CL) is a serious public health that affects more than 98 countries, putting 350 million people at risk. There are no vaccines that have been proven to prevent CL, and the treatment relies on drugs that often have severe side effects, justifying the search for new antileishmanial treatments. In the present investigation, it is demonstrated that 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-methylbenzyl)-1H-1,2,3-triazole (7k) presents significant antileishmanial activity (IC50 of 7.4 μmol L−1 and 1.6 μmol L−1 for promastigote and amastigote forms, respectively), low cytotoxicity against macrophage cells (IC50 of 211.9 μmol L−1), and a selective index of 132.5. Under similar conditions, compound 7k outperformed glucantime and pentamidine, two commonly used drugs in clinics. In vivo assays on CL-infected female BALB/c mice demonstrated that compound 7k had activity similar to intralesional glucantime when administered orally, with decreased lesion and parasitic load, and a low systemic toxic effect. Given the importance of understanding the relationship between compound structure and biological activity in the research and development of new drugs, the development of a quantitative structure-activity relationship (QSAR) model for the leishmanicidal activity presented by the eugenol derivatives with 1,2,3-triazole functionalities is also described herein. This study demonstrates the therapeutic potential of orally active eugenol derivatives against CL and provides useful insights into the relationship between the chemical structures of triazolic eugenol derivatives and their biological profile.

Chemical Composition and Potential of Eucalyptus camaldulensis Dehnh. Essential Oil and Its Major Components as Anti-inflammatory and Anti-leishmanial Agent

The present study evaluated cytotoxic, anti-inflammatory, and anti-leishmanial properties of essential oil (EO) from fresh foliage of Eucalyptus camaldulensis Dehnh., and its major constituent compounds− 1,8-cineole, β-pinene and α-pinene. The chromatographic analysis of the hydrodistilled EO using gas chromatography-mass spectrometry (GC/MS) revealed the presence of 25 compounds which constituted 99.45% of EO. The EO comprised of 36% monoterpenoid hydrocarbons and 22.3% oxygenated monoterpenes. The most abundant constituent was 1,8-cineole (17.1%) followed by β-pinene (16.5%). In addition, significant quantities of β-eudesmol (10.9%), limonene (9.5%), and α-pinene (7.9%) were observed. Cell cytotoxicity concentration was observed to be highest in 1,8-cineole (CC50 > 640 µg/mL), followed by α-pinene (CC50 > 320 µg/mL), β-pinene (CC50 > 160 µg/mL) and EO (CC50 > 20 µg/mL). Investigation of anti-inflammatory potential by carrageenan-induced rat paw edema model revealed maximum inhibition in α-pinene (85.6% at 500 mg/kg body wt. and 81% at 250 mg/kg body wt.) after 3 h, which was comparable to indomethacin (positive control). Among the EO and its components, β-pinene exhibited maximum anti-leishmanial potential with IC50 of 2.57 ± 0.15 mL. The study concluded that E. camaldulensis EO possesses significant anti-inflammatory and anti-leishmanial activity, thus suggesting the use of EO and its major constituents as a green drug that is a safer alternative to synthetic compounds.

Microwave assisted Biology-Oriented Drug Synthesis (BIODS) of new N,N′-disubstituted benzylamine analogous of 4-aminoantipyrine against leishmaniasis – In vitro assay and in silico-predicted molecular interactions with key metabolic targets

Biology-Oriented Drug Synthesis (BIODS) deals with the simple chemical transformations on the commercially available drugs in order to enhance their new and diversified pharmacological profile. It opens new avenues for the rapid development of drug candidates for neglected tropical diseases (NTDs). Leishmaniasis is one of the NTDs which spread by the bite of sandflies (plebotomine). It ranges from cutaneous self-healing leishmaniasis to life threatening visceral leishmaniasis, known as kala-azar. The current treatment options include the use of pentamidine, miltefosine, and amphotericin B drugs. Unfortunately, all currently available drugs are associated with adverse effects, such as severe nephron- and cardiotoxicity, pancreatitis, and hepatotoxicity. This warrants the development of new drugs against leishmaniasis. Moreover, emergence of resistance against the current medications further worsens the conditions. With this objective, new N, N′-disubstituted benzylamine derivatives of ampyrone (4-aminoantipyrine) were synthesized by using ultrasonication, and microwave assistance. All derivatives were found to be new, except 1, 4, and 11. All the compounds were evaluated for their anti-leishmanial activity, and cellular cytotoxicity. Among them, compounds 4, 5, 8, and 9 showed a significant anti-leishmanial activity in vitro, in comparison to standard drug, miltefosine (IC50 = 25.78 ± 0.2 µM). These compounds were also docked against various metabolic enzymes to predict their interactions and mechanism of action, and were found to act via targeting important enzymes of various metabolic pathways.

Assessment of in vitro and in vivo effect of Quercetin 3-Glucoside, Oxyresveratrol and Quercetin O-Hexoside against Leishmania tropica

The aim was to scrutinize the in vivo and in vitro activities against Leishmania tropica with compounds of Oxyresveratrol, Quercetin O-Hexoside, and Quercetin 3-Glucoside. The in vitro outcomes against Leishmania were analyzed for 24-48 hours on L. tropica KWH23 promastigotes with compounds materials having 50 - 200 µg/mL concentration with negative control and standard drug Amphotericin B. The compounds were analyzed in L. tropica infected BALB/c mice against Leishmania tropica. The Quercetin 3-Glucoside shows mean inhibition of extracellular promastigotes after 48 hours at 50, 100, 150, 200 µg/mL were 91.02 ± 0.12, 94.50 ± 0.07, 96.15 ± 0.17 and 97.01 ± 0.08 % respectively. In BALB/c mice, the intracellular amastigotes were 91% cured at 200 µg/mL and mean lesion size decreased to 0.41 ± 0.21 mm (p < 0.01). The result shows that Quercetin 3-Glucoside possesses significant anti-leishmanial activity.

In Vitro Antileishmanial and Antischistosomal Activities of Anemonin Isolated from the Fresh Leaves of Ranunculus multifidus Forsk.

Leishmaniasis and schistosomiasis are neglected tropical diseases (NTDs) infecting the world’s poorest populations. Effectiveness of the current antileishmanial and antischistosomal therapies are significantly declining, which calls for an urgent need of new effective and safe drugs. In Ethiopia fresh leaves of Ranunculus multifidus Forsk. are traditionally used for the treatment of various ailments including leishmaniasis and eradication of intestinal worms. In the current study, anemonin isolated from the fresh leaves of R. multifidus was assessed for its in vitro antileishmanial and antischistosomal activities. Anemonin was isolated from the hydro-distilled extract of the leaves of R. multifidus. Antileishmanial activity was assessed on clinical isolates of the promastigote and amastigote forms of Leishmania aethiopica and L. donovani clinical isolates. Resazurin reduction assay was used to determine antipromastigote activity, while macrophages were employed for antiamastigote and cytotoxicity assays. Antischistosomal assays were performed against adult Schistosoma mansoni and newly transformed schistosomules (NTS). Anemonin displayed significant antileishmanial activity with IC50 values of 1.33 nM and 1.58 nM against promastigotes and 1.24 nM and 1.91 nM against amastigotes of L. aethiopica and L. donovani, respectively. It also showed moderate activity against adult S. mansoni and NTS (49% activity against adult S. mansoni at 10 µM and 41% activity against NTS at 1 µM). The results obtained in this investigation indicate that anemonin has the potential to be used as a template for designing novel antileishmanial and antischistosomal pharmacophores.

Identification of Suitable Agents against Adenine Phosphoribosyl Transferase for the Management of Leishmaniasis: Synthesis, Characterization and Computational Studies

A leishmaniasis is a group of diseases attributable to protozoan parasites of the genus Leishmania. It is a potential disease mostly occurring in developing nations. Various quinoline substituted derivatives (11a-f, 12a-f, and 13a-f) were synthesized by refluxing amino quinolines with an equivalent number of different alkylaminoethyl chlorides and evaluated for their in vitro antileishmanial activity against promastigotes forms of Leishmania donovani by using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] reduction assay. Compounds 11f (IC50 = 13.61μg/mL), 12f (IC50 = 11.92 μg/mL) and 13f (IC50 =10.41 μg/mL) have shown significant antileishmanial activity when compared with standard sitamaquine (IC50= 10.09 μg/mL). Furthermore, the molecular docking analysis targeting adenine phosphoribosyltransferase of Leishmania donovani exhibits significant binding interactions. In silico, ADMET predictions revealed that these compounds, i.e., 11f, 12f, and 13f, demonstrated good absorption as well as solubility characteristics with good drug-likeness and drug score values compared to the standard drug.

Antileishmanial Activity of Cassia fistula L., Morus nigra L. and Ziziphus jujuba Mill., Plant Extracts

Aim: To investigate the different antileishmanial activities of extracts of Cassia Fistula L., Morus Nigra L. and Ziziphus Jujuba Mill.&#x0D; Methodology: In this method, three (03) plants having concentrations between 500 – 2000 µg/mL were subjected to KWH23 strains of L. tropica in which Standard drug was Amphotericin B and have negative control for 24 – 48 hours. To check the in-vivo studies, plant extract was tested on BALB/c mice (Iqbal et al., 2016).&#x0D; Results: It showed that inhibition (mean) of KWH23 strains at 500, 1000, 1500, 2000 µg/mL after 48 hours were 92.1 ± 0.02, 95.00 ± 0.05, 97.09 ± 0.07 and 98.05 ± 0.05 % respectively. It decreased the lesion size (mean) from 0.8 ± 0.1 mm to 0.40 ± 0.2 mm having significance value p &lt; 0.01 after 8th week, and cure at 200 mg/Kg against intracellular amastigotes in BALB/c mice was 90.00% (95% Cl = 80.05 – 97.00).&#x0D; Conclusion: The result shows that Ziziphus jujuba Mill. leaves possess significant antileishmanial activity.

Novel phenanthridine amide analogs as potential anti-leishmanial agents: In vitro and in silico insights

In the current work, sixteen novel amide derivatives of phenanthridine were designed and synthesized using 9-fluorenone, 4-Methoxy benzyl amine, and alkyl/aryl acids. The characterization of the title compounds was performed using LCMS, elemental analysis, 1HNMR, 13CNMR and single crystal XRD pattern was also developed for compounds A8. All the final analogs were screened in vitro for anti-leishmanial activity against promastigote form of L. infantum strain. Among the tested analogs, four compounds (A-06, A-11, A-12, and A-15) exhibited significant anti-leishmanial activity with EC50 value ranges from 8.9 to 21.96 μM against amastigote forms of tested L. infantum strain with SI ranges of 1.0 to 4.3. From the activity results it was found that A-11 was the most active compound in both promastigote and amastigotes forms with EC50 values 8.53 and 8.90 µM respectively. In-silico ADME prediction studies depicted that the titled compounds obeyed Lipinski's rule of five as that of the approved marketed drugs. The predicted in-silico toxicity profile also confirmed that the tested compounds were non-toxic. Finally, molecular docking and molecular dynamics study was also performed for significantly active compound (A-11) in order to study it’s putative binding pattern at the active site of the selected leishmanial trypanothione reductase target as well as to understand the stability pattern of target-ligand complex for 100 ns. Single crystal XRD of compound A-08 revealed that the compound crystallizes in monoclinic C2/c space group and showed interesting packing arrangements.

Critical Antileishmanial in vitro Effects of Highly Examined Gold Nanoparticles.

IntroductionThe current therapeutic armory for visceral leishmaniasis (VL) caused by Leishmania donovani complex is inadequate, coupled with serious limitations. Combination therapy has proved ineffective due to mounting resistance; however, the search for safe and effective drugs is desirable, in the absence of any vaccine. There is a growing interest in the application of nanoparticles for the therapeutic effectiveness of leishmaniasis. Aimed in this direction, we assessed the antileishmanial effect of gold nanoparticles (GNP) against L. donovani in vitro.MethodsGNP were synthesized and characterized for particle size by dynamic light scattering (DLS) and atomic force microscopy (AFM) and for optical properties by UV-visible spectroscopy. Cytotoxicity of GNP was measured by the MTT proliferation assay. The antileishmanial activity of the nanoparticles was evaluated against L. donovani promastigotes and macrophage-infected amastigotes in vitro.ResultsGNP showed a strong SPR peak at 520 nm and mean particle size, polydispersity index (PDI), and zeta potential of 56.0 ± 10 nm, 0.3 ± 0.1 and −27.0 ± 3 mV, respectively. The GNPs were smooth and spherical with a mean particle diameter of 20 ± 5 nm. Nanoparticles [1.2–100 µM] did not reveal any cytotoxicity on RAW 264.7 murine macrophage cell line, but exerted significant activity against both promastigotes and amastigote stages of L. donovani with 50% inhibitory concentrations (IC50) of 18.4 ± 0.4 µM and 5.0 ± 0.3 µM, respectively. GNP showed significant antileishmanial activity with deformed morphology of parasites and the least number of surviving promastigotes after growth reversibility analysis.ConclusionGNP may provide a platform to conjugate antileishmanial drugs onto the surface of nanoparticles to enhance their therapeutic effectiveness against VL. Further work is warranted, involving more in-depth mechanistic studies and in vivo investigations.

In vitro efficacy of polymer coated miltefosine drug against leishmania tropica.

Polymer based nanoparticles for drug delivery is an alternative approach to overcome drug resistance and drug toxicity especially for cutaneous leishmaniasis treatment. The present study shows synthesis and characterization of Miltefosine loaded chitosan nanoparticles (MFS-CNPs). The synthesized MFS-CNPs were experimented to evaluate the in vitro cytotoxicity and efficacy of the synthesized drug loaded nanoparticles by hemolysis assay and 3-(4, 5- dimethylthiazol-2-yl)-2,5-diphenyletetrazolium bromide (MTT) assay. MFS-CNPs were synthesized by ionic gelation method with sodium tripolyphosphate. The characterization of synthesized NPs was performed to observe the surface morphology, encapsulation efficacy, drug loading content, average size, and zeta potential. In vitro MTT assay was performed to calculate half maximal inhibitory concentration value of synthesized nanoparticles against promastigotes and axenic amastigotes of L. tropica. By using Scanning electron microscope, MFS-CNPs displayed spherical shape having a mean size of 70nm along with high EE (97%), DLC (91%) and negative surface charge (-28.0mV). Dynamic light scattering shows the average size of NPs was 91.4nm. Moreover, less than 5% hemolytic activity was observed in MFS-CNPs as compared to free MFS in different concentrations (100μg/ml, 125μg/ml, 150μg/ml).It was observed that the effect of MFS-CNPs and free MFS on both forms of the parasite was dose and time dependent. However, the cytotoxic effects of MFS-CNPs were more salient than free MFS on both forms of L. tropica. Using MTT assay, free MFS presented low efficacy at higher concentrations (30µg/ml) with 21.4 ± 1.3 and 20.5 ± 1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72h incubation. While MFS-CNPs showed strong antileishmanial effects on both forms of L. tropica (11 ± 0.3 and 14 ± 0.8) mean viability rate after 72h incubation at (30µg/ml). When analyzed statistically by the software, Graph Pad Prism version 5, the IC50 value of MFS-CNPs (0.0218 ± 0.01µg/ml) against promastigotes was effective than free MFS (0.3548 ± 0.17µg/ml). Similarly, MFS-CNPs activity against axenic amastigotes (0.1008 ± 0.02µg/ml) was potent than free MFS (0.5320 ± 0.21µg/ml). Hence, MFS-CNPs exhibited significant antileishmanial activity in vitro. In conclusion, MFS-CNPs manifested enhanced in vitro Leishmanicidal and less hemolytic activity; however more studies are needed to support its efficacy in both animal and human cutaneous leishmaniasis.

Diterpenes and sterols from the Red Sea soft coral Sarcophyton trocheliophorum and their cytotoxicity and anti-leishmanial activities

The ethyl acetate and dichloromethane-soluble fractions, from a soft coral Sarcophyton trocheliophorum total methanolic extract, exhibited significant anti-leishmanial and cytotoxic activities. These active fractions yielded a new cembranoid diterpene (1), two known analogues [sarcotrocheliol (2) and sarcophine (3)], and two sterols [(24S)-24-methylcholesterol (4) and gorgosterol (5)]. The structure of the new diterpene (1) was determined via a detailed analysis of its spectroscopic data. Compounds 3 and 5 demonstrated noticeable cytotoxicity on A549 (IC50 17.4 ± 1.9 µg/ml) and HepG2 (IC50 17.7 ± 1.5 µg/ml) cell lines, respectively. None of the isolates 1‒5 showed detectable anti-leishmanial activity (IC50 >100 µg/ml).

Evidence for Reversal of Immunosuppression by Homeopathic Medicine to a Predominant Th1-type Immune Response in BALB/c Mice Infected with Leishmania donovani.

Visceral leishmaniasis (VL) is a neglected tropical disease that is fatal if treatment is not given. The available chemotherapeutic options are unsatisfactory, and so complementary therapies like homeopathy might be a promising approach. A nosode from a pure axenic culture of Leishmania donovani was prepared and screened for its anti-leishmanial potential both in an in-vitro and an in-vivo experimental approach. Leishmania donovani amastigote promastigote nosode (LdAPN 30C) exhibited significant anti-leishmanial activity against the promastigote forms of Leishmania donovani and was found to be safe. A study conducted on VL-infected mice revealed that LdAPN 30C resolved the disease by modulating the host immune response toward the Th1 type through upregulating the pro-inflammatory cytokines (IFN-γ and IL-17) and inducing nitric oxide (NO) levels in the infected macrophages. The hepatic parasite load was also found to be significantly decreased. The nosode was found to be safe, as no histological alterations in the liver or kidney were observed in the animals treated with the LdAPN 30C. This is the first study in which an axenic culture of Leishmania donovani has been used for the preparation of a homeopathic medication. The study highlights the anti-leishmanial and immunomodulatory potential of a homeopathic nosode in experimental VL.

Curcuma longa Mediated Synthesis of Copper Oxide, Nickel Oxide and Cu-Ni Bimetallic Hybrid Nanoparticles: Characterization and Evaluation for Antimicrobial, Anti-Parasitic and Cytotoxic Potentials

Nanoparticles have long been known and their biomedical potent activities have proven that these can provide an alternative to other drugs. In the current study, copper oxide, nickel oxide and copper/nickel hybrid NPs were biosynthesized by using Curcuma longa root extracts as a reducing and capping agent, followed by characterization via UV-spectroscopy, Fourier transformed infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermo galvanometric analysis (TGA), and band gap. FTIR spectroscopy shows the availability of various functional groups and biomolecules such as carbohydrate, protein, polysaccharides, etc. The EDX peak confirmed that the elemental nickel and copper were present in large quantity in the analyzed sample. Scanning electron micrographs showed that the synthesized CuO-NPs and NiO-NPs were polyhedral uniform and homogeneous in morphology, while the copper/nickel hybrid NPs were well dispersed, spherical in shape, and uniform in size. TEM micrographs of CuO-NPs had 27.72 nm, NiO had 23.13 nm and, for their hybrid, the size was 17.38 nm, which was confirmed respectively. The CuO and NiO NPs possessed spherical- to multi-headed shapes, while their hybrid showed a complete spherical shape, small size, and polydispersed NPs. The XRD spectra revealed that the average particle size for CuO, NiO, and hybrid were 29.7 nm, 28 nm and 27 nm, respectively. Maximum anti-diabetic inhibition of (52.35 ± 0.76: CuO-NPs, 68.1 ± 0.93: NiO-NPs and 74.23 ± 0.42: Cu + Ni hybrids) for α-amylase and (39.25 ± 0.18 CuO-NPs, 52.35 ± 1.32: NiO-NPs and 62.32 ± 0.48: Cu + Ni hybrids) for α-glucosidase were calculated, respectively, at 400 µg/mL. The maximum antioxidants capacity was observed as 65.1 ± 0.83 μgAAE/mg for Cu-Ni hybrids, 58.39 ± 0.62 μgAAE/mg for NiO-NPs, and 52.2 ± 0.31 μgAAE/mg for CuO-NPs, respectively, at 400 μg/mL. The highest antibacterial activity of biosynthesized NPs was observed against P. aeuroginosa (28 ± 1.22) and P. vulgaris (25 ± 1.73) for Cu + Ni hybrids, respectively. Furthermore, the antibiotics were coated with NPs, and activity was noted. Significant anti-leishmanial activity of 60.5 ± 0.53 and 68.4 ± 0.59 for Cu + Ni hybrids; 53.2 ± 0.48 and 61.2 ± 0.44 for NiO-NPs; 49.1 ± 0.39 and 56.2 ± 0.45 for CuO-NPs at 400 μg/mL were recorded for promastigote and amastigotes, respectively. The biosynthesized NPs also showed significant anti-cancerous potential against HepG2 cell lines. It was concluded from the study that NPs are potential agents to be used as an alternative to antimicrobial agents.

PHYTOCHEMICAL AND BIOLOGICAL STUDIES ON AGERATUM CONYZOIDES L.

The ultrasonic assisted extraction method is more efficient as compared with normal conventional methods. The current study was aimed to perform ultrasonic assisted extraction of Ageratum conyzoides. Natural solvents such as n-hexane, dichloromethane, methanol and ethyl acetate were utilized for the purpose. Phytochemical studies indicated terpenoids, alkaloids, sterols, flavonoids, cardiac glycosides, saponins and coumarins as major constituents. The biological potential of various fractions was also determined in different extracts. In antibacterial and antifungal assays, a reasonable activity was obtained. All the extracts were also screened for Leishmanicidal and cytotoxic potential beside Leishmania chief promastigotes and 3T3 cancer cells, respectively. The methanol and ethyl acetate extracts showed significant antileishmanial activities i.e. IC50 5.61 ± 0.50µg/ml and IC50 23.21 ± 0.61µg/ml, respectively.&#x0D;