Good Antileishmanial Activity Research Articles

Cytotoxicity, leishmanicidal, and antioxidant activity of biosynthesised zinc sulphide nanoparticles using Phoenix dactylifera

The synthesis of zinc sulphide nanoparticles (ZnS NPs) using a green approach was explored. The resulting nanoparticles (NPs) were characterised by UV–vis spectroscopy, scanning and transmission electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. The leishmanicidal, cytotoxic and antioxidant activity of the resulting synthesised ZnS NPs (<70 nm) were evaluated against Leishmania major (L. major) promastigotes and amastigotes by MTT assay and using a macrophage model. The ZnS NPs were able to counteract the effects of oxidative metabolites as demonstrated by the oxidant activity. The IC50 value of butylated hydroxyanisole was 26.04 µg/ml as compared with the IC50 for ZnS NPs (90.95 µg/ml). The NPs displayed no cytotoxicity for the murine macrophaghes as the selectivity index (SI) fell into the safety range (SI ≥ 10). These nanomaterials exhibited good antileishmanial activity against the L. major stages that were comparable to that of Glucantime, the drug of choice. The IC50 values of ZnS NPs and Glucantime against amastigotes were 11.59 ± 2.51 and 4.95 ± 2.51 μg/ml, respectively. The IC50 values for ZnS NPs and Glucantime versus promastigote were 29.81 ± 3.15 and 14.75 ± 4.05 μg/ml, respectively. Further investigation is essential to explore the biological effects of ZnS NPs on animal and/or clinical models.

In vivo antileishmanial activity and histopathological evaluation in Leishmania infantum infected hamsters after treatment with a furoxan derivative

N-oxide derivatives compounds such as furoxan and benzofuroxan are promising scaffolds for designing of new antileishmanial drugs. A series of furoxan (1,2,5-oxadiazole 2-N-oxide) (compounds 4a-b, and 14a-f) and benzofuroxan (benzo[c][1,2,5]oxadiazole1-N-oxide) (compounds 8a-c) derivatives were evaluated against in vitro cultured L. infantum promastigotes and amastigotes. The compounds exhibited activity against promastigote and intracellular amastigote forms with EC50 values ranging from 2.9 to 71.2μM and 2.1 to 18.2μM, respectively. The most promising compound, 14e, showed good antileishmanial activity (EC50=3.1μM) against intracellular amastigote forms of L. infantum with a selectivity index, based on murine macrophages (SI=66.4), almost 3-times superior to that presented by the standard drug amphotericin B (AmpB). The efficacy of 14e to eliminate the parasites in vivo was also demonstrated. Treatment of L. infantum-infected hamsters with compound 14e at 3.0mg/Kg/day led to a meaningful reduction of parasite load in spleen (49.9%) and liver (54.2%), respectively; these data were corroborated by histopathological analysis, which also revealed reduction in the number of inflammatory cells in the liver of the treated animals. Moreover, histological analysis of the spleen and kidney of treated animals did not reveal alterations suggestive of toxic effects. The parasite load reduction might be related to NO production, since this molecule is a NO-donor. We observed neither side effects nor elevation of hepatic/renal biomarker levels in the plasma. The data herein presented suggest that the compound should be considered in the development of new drugs for treatment of visceral leishmaniasis.

In Vitro Evaluation of Antileishmanial Activity of Computationally Screened Compounds against Ascorbate Peroxidase To Combat Amphotericin B Drug Resistance.

In visceral leishmaniasis (VL), the host macrophages generate oxidative stress to destroy the pathogen, while Leishmania combats the harmful effect of radicals by redox homeostasis through its unique trypanothione cascade. Leishmania donovani ascorbate peroxidase (LdAPx) is a redox enzyme that regulates the trypanothione cascade and detoxifies the effect of H2O2 The absence of an LdAPx homologue in humans makes it an excellent drug target. In this study, the homology model of LdAPx was built, including heme, and diverse compounds were prefiltered (PAINS, ADMET, and Lipinski's rule of five) and thereafter screened against the LdAPx model. Compounds having good affinity in terms of the Glide XP (extra precision) score were clustered to select diverse compounds for experimental validation. A total of 26 cluster representatives were procured and tested on promastigote culture, yielding 12 compounds with good antileishmanial activity. Out of them, six compounds were safer on the BALB/c peritoneal macrophages and were also effective against disease-causing intracellular amastigotes. Three out of six compounds inhibited recombinant LdAPx in a noncompetitive manner and also demonstrated partial reversion of the resistance property in an amphotericin B (AmB)-resistant strain, which may be due to an increased level of reactive oxygen species (ROS) and decrease of glutathione (GSH) content. However, inhibition of LdAPx in resistant parasites enhanced annexin V staining and activation of metacaspase-like protease activity, which may help in DNA fragmentation and apoptosis-like cell death. Thus, the present study will help in the search for specific hits and templates of potential therapeutic interest and therefore may facilitate the development of new drugs for combination therapy against VL.

Evaluation of Zanthoxylum armatum Roxb for in vitro biological activities

Zanthoxylum armatum fruits are used traditionally as a spice in various food preparations. The aim of this study was analysis of antimicrobial, cytotoxic, phytotoxic, insecticidal, and anti-leishmanial activity. The crude extract showed 86 ± 10% antifungal activity (Agar tube dilution method) against Trichophyton longifusis while n-hexane, chloroform, and aqueous-methanol fractions inhibited this pathogen by 90 ± 7, 85 ± 10 and 70 ± 9% respectively. The n-hexane and aqueous-methanol fraction also, respectively, showed 40 ± 10 and 87 ± 9% inhibition of Microsporum canis. Chloroform fraction also displayed antifungal activity against Aspergillus flavus (60 ± 10%) and aqueous-methanol fraction against F. solani (40 ± 8%). The crude ethanolic extract and its chloroform and aqueous-methanol fraction exhibited significant toxicity (Brine shrimps lethality assay) against brine shrimps having LC50 value of 6.66 ± 1.1, 21.4 ± 3.3 and 29.6 ± 3.9 μg/ml, respectively. The crude ethanolic extract and its n-hexane soluble portion exhibited good anti-leishmanial activity (well serial dilution method) each having IC50 values of 50 ± 5 μg/ml. The crude extract and various fractions possessed excellent herbicidal activity (Lemna minor assay), and caused more than 90% inhibition of the plant growth at 1000 μg/mL. The ethanolic extract, n-hexane and chloroform soluble portions caused 90% mortality in insecticidal activity (direct contact method) of Rhyzopertha dominica. The ethanolic extract and its n-hexane soluble portion, respectively, caused 80 and 90% mortality of Callosobruchus analis. The present study showed that the tested fruit extracts of Z. armatum exhibited strong antifungal, cytotoxic, phytotoxic, insecticidal, and anti-leishmanial effects.

Synthesis, antileishmanial activity and QSAR studies of 2-chloro- N -arylacetamides

We describe herein the synthesis and evaluation of the antileishmanial activity against promastigote forms of Leishmania amazonensis and cytotoxicity to murine macrophages of a series of 2-chloro-N-arylacetamide derivatives. All compounds were active, except one (compound 3). Compound 5 presented the most promising results, showing good antileishmanial activity (CI50=5.39±0.67 µM) and moderate selectivity (SI=6.36), indicating that further development of this class is worthwhile. Preliminary QSAR studies, although not predictive, furnished some insights on the importance of electronic character of aryl substituent to biological activity, as well as an indirect influence of hydrophobicity on activity.

Bioactivity of Phycocolloids against the Mediterranean Protozoan Leishmania infantum: An Inceptive Study

Sulfated polysaccharides from marine macroalgae have been shown to possess a variety of biological activities against fungi, bacteria, viruses, and protozoa. In this study, the in vitro activity of algal polysaccharides against Leishmania infantum (Kinetoplastida: Trypanosomatidae) was investigated. The polysaccharides were extracted from different macroalgae of the Mediterranean Sea: Chaetomorpha linum, Agardhiella subulata, Gracilaria viridis, Gracilaria bursa-pastoris, Hypnea cornuta, Sargassum muticum, and Undaria pinnatifida. Preliminary results showed a good anti-leishmanial activity of the investigated species, encouraging the focus on their use as natural resources in order to match integrated management strategies for the employment of local macroalgae.

Antileishmanial effect of new indeno-1,5-naphthyridines, selective inhibitors of Leishmania infantum type IB DNA topoisomerase

Visceral leishmaniasis is a neglected disease of poor and developing countries. The current therapeutic approach is based on pentavalent antimonial (SbV) drugs and amphotericin B, both nephrotoxic and parenterally administered drugs. Therefore, there is a real need of new antileishmanial drugs. Eukaryotic type I DNA topoisomerases (TopIB) have been identified as druggable targets against leishmaniasis. These enzymes are involved in solving topological problems generated during replication, transcription and recombination of DNA. Leishmanial TopIB is a unique heterodimeric protein structurally different than that found in the mammalian host, thus making it an interesting target for drug discovery. Tetrahydro indeno-1,5-naphthyridines 5 and indeno[1,5]naphthyridines 6 were synthesized. The inhibition of Leishmania and human TopIB of these polycyclic heterocycles were studied and their antileishmanial activity on promastigotes and amastigote-infected splenocytes of Leishmania infantum were evaluated. In this regard, it is noteworthy that some of the prepared heterocycles, as compounds 6b, 6i and 5 h, showed selective inhibition of LtopIB while no inhibition of hTopIB was observed at evaluated conditions. In addition, the cytotoxic effects of newly synthesized compounds were assessed on host murine splenocytes in order to calculate the corresponding selective indexes (SI). Tetrahydro indeno-1,5-naphthyridines 5e and 5h showed good antileishmanial activity (IC50 values of 0.67 ± 0.06 and 0.54 ± 0.17 μM) with similar activity than the standard drug amphotericin B (0.32 ± 0.05 μM) and even tetrahydro indeno-1,5-naphthyridine 5h showed higher (SI) towards L. Infantum amastigotes. Likewise, in the family of indeno-[1,5]-naphthyridines 6, compound 6b showed good antileishmanial activity (IC50 value 0.74 ± 0.08 μM) and higher selective index (SI) towards L. Infantum amastigotes than amphotericin B.

Phytochemical screening of the exudate of Aloe otallensis and its effect on Leishmania donovani

Objective: To evaluate the antileishmanial activity of methanolic extract of Aloe otallensis (A. otallensis) on the promastigote stage of Leishmania donovani (L. donovani) as compared to standard drugs and to screen its phytochemical constituents. Methods: Phytochemical screening was done by using the method mentioned by Evans and Trease on methanolic extract of the exudates of Aloe otallensis leaves. The extract was also evaluated for in vitro antileishmanial activity against L. donavani which is found from the Parasitology Unit of Black Lion Hospital. The result was compared to standard drugs of sodium stibogluconate, milfostin and paramomycin. Results: The extract has a good antileishmanial activity with an IC50 of 0.123 0 μg/mL on L. donovani (AM 563). The experimental data showed that relatively it had better activity than paramomycin and milfostin but less activity than sodium stibogluconate. The data analyses were done by GraphPad Prism version 5 software after it was read by ELISA reader at the wave length of 650 nm. The phytochemical screening of the exudates of A. otallensis showed the presence of phenol, alkaloid and saponin. Conclusions: The methanol extract of the exudates of A. otallensis has a good antileishmaniasis activity and this may be attributed to phenol, alkaloid and saponin present in the plant. But it needs further analysis for the conformation of which constituent presents in high concentration to know which one has the strongest effect.

Screening of Aloe otallensis Exudate and Its Effect on Leishmania aethiopica

Background and objectives: The different Aloaceae plant extracts have been tested and found to contain components with anti leishmanial activity. Our study was conducted to assure anti leishmanial activity of the methanol extract of Aloe otallensis on the promastigot stage of Leishmania aethiopica as compared to currently used drugs and also tried to screen its phytochemical constitutes. Methods: Aloe otallensis leaf exudate was extracted by using methanol solvent and phytochemical screening was done using the method mentioned by Trease and Evans as well as the extract was evaluated for in vitro anti leishmanial activity against Leishmania aethiopica which was taken from the Black Lion Specialized Hospital parasitology unit. The result was compared with currently used drug like; Sodium stibogluconate, milfostin and paramomycin. Result: The extract has a good anti leishmanial activity with an IC50 of 0.041 μg/mL on L. aethiopica (LDC/134). The experimental result shows that the extract has better anti leishimanial activity on L. aethiopica than paramomycin and milfostin but less activity than sodium stibogluconate. The data analyses was done by pad graph prison version 5 software after it was read by ELISA reader at the wave length of 650 nm. The phytochemical screening of aloe otallensis exudate showed the presence of phenol, alkaloid and saponin. Conclusion: Aloe otallensis exudate methanol extract was found to have a good anti leishmaniasis activity against L. Aethiopica and this may be attributed to phenol, alkaloid and saponin present in the plant. Even though this is our conclusion it needs further investigations to confirm which constituent(s) is/are responsible for such effect and at how many concentrations.

Cinnamic Acid Bornyl Ester Derivatives from Valeriana wallichii Exhibit Antileishmanial In Vivo Activity in Leishmania major-Infected BALB/c Mice.

Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major promastigotes revealed that compounds 1 and 2 induce mitochondrial swelling. Subsequent studies on Leishmania major promastigotes showed the loss of mitochondrial transmembrane potential (ΔΨm) as a putative mode of action. As the cinnamic acid bornyl ester derivatives 1 and 2 had exhibited antileishmanial activity in vitro, and compound 2 in Leishmania major-infected BALB/c mice in vivo, they can be regarded as possible lead structures for the development of new antileishmanial therapeutic approaches.

Aspernolides F and G, new butyrolactones from the endophytic fungus Aspergillus terreus

Two new butyrolactones: aspernolides F (6) and G (7), together with three stigmasterol derivatives: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), and stigmasta-4,6,8(14), 22-tetraen-3-one (3), two meroterpenoids: terretonin A (4) and terretonin (5), and a butyrolactone derivative: butyrolactone VI (8) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were determined by spectroscopic means (1D, 2D NMR, and HRESIMS), as well as optical rotation measurement and comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. Compound 1 displayed a potent activity against MRSA and C. neoformans with IC50 values of 0.96μg/mL and 4.38μg/mL, respectively compared to ciprofloxacin (IC50 0.07μg/mL) and amphotericin B (IC50 0.34μg/mL), respectively. While, 6 showed good activity against C. neoformans (IC50 5.19μg/mL) and mild activity against MRSA (IC50 6.39μg/mL). Moreover, 1 and 2 exhibited very good anti-leishmanial activity towards L. donovani with IC50 values of 4.61 and 6.31μg/mL, respectively and IC90 values of 6.02 and 16.71μg/mL, respectively.

Developing imidazole analogues as potential inhibitor for Leishmania donovani trypanothione reductase: virtual screening, molecular docking, dynamics and ADMET approach

Visceral leishmaniasis (VL) affects Indian subcontinent, African and South American continent, and it covers 70 countries worldwide. Visceral form of leishmaniasis is caused by Leishmania donovani in Indian subcontinent which is lethal if left untreated. Extensive resistance to antileishmanial drugs such as sodium stibogluconate, pentamidine and miltefosine and their decreased efficacy has been reported in the endemic region. Amphotericin B drug has shown good antileishmanial activity with significant toxicity, but its cost of treatment has limited the outreach of this treatment to affected people living in endemic zone. So, there is an urgent need to identify new antileishmanial drugs with excellent activity and minimal toxicity issues. Trypanothione reductase, a component of antioxidant system, is necessary for parasite growth and survival to raise infection. To develop potential inhibitor, we docked nine hundred and eighty-four 5-nitroimidazole analogues along with clomipramine which is a well-known inhibitor for TR. Total one hundred and forty-seven 5-nitroimidazole analogues with better docking score than clomipramine were chosen for ADMET and QikProp studies. Among these imidazole analogues, total twenty-four imidazole analogues and clomipramine were chosen on the basis of their ADMET, QikProp, and prime MM-GBSA study. Later on, two analogues with best MM-GBSA dG bind were undergone molecular dynamic simulation to ensure protein–ligand interactions. Using above approach, we confirm that ethyl 2-acetyl-5-[4-butyl-2-(3-hydroxypentyl)-5-nitro-1H-imidazol-1-yl]pent-2-enoate can be a drug candidate against L. donovani for the treatment of VL in the Indian subcontinent.

Evaluation of antileishmanial, antibacterial and brine shrimp cytotoxic potential of crude methanolic extract of Herb Ocimum basilicum (Lamiacea)

ObjectiveTo collect and screen for ethnopharmacological properties (antileishmanial, antibacterial and brine lethality assays) of medicinal plant Ocimum basilicum from Peshawar region (34.008 Latitude and 71.57 altitudes). MethodsIn the present study a general antileishmanial activity against Leishmania tropica strain was carried out. The antibacterial potential of the plant was performed against 06 gram positive and 06 gram negative bacteria. Brine shrimp cytotoxicity assay at different concentrations were investigated. ResultsThe anti-promastigotes profile of the plant showed good antileishmanial activity exhibited LC50 value 21.67 μg/mL. The result for gram positive antibacterial activity revealed that the O. basilicum leaves extract possesses significant inhibitory activity at highest two concentrations ranging from 20.66 ± 0.31 to 31.86 ± 0.80 for Clostridium perfringens type C and Bacillus subtitilis, respectively, as compared to the gentamycin (27.36 ± 0.55 and 21.80 ± 0.72, respectively). For gram negative bacteria good activity was observed. A highest zone of inhibition was recorded for Pseudomonas aeroginosa (28.83 ± 0.28) at the highest concentration (10 mg/mL). The LC50 value obtained for brine shrimp lethality assay was 91.56 μg/mL. ConclusionThe herb basil possesses effective cidal activities which make this plant a good candidate for the isolation of antiprotozoal and antibacterial compounds which may lead to the development of novel drug.

Bioactivity and chemical composition of the essential oil from the leaves of Guatteria australis A.St.-Hil

Essential oil from the leaves of Guatteria australis was obtained by hydrodistillation, analyzed by Gas Chromatography coupled to Mass Spectromery (GC–MS) and their antiproliferative, antileishmanial, antibacterial, antifungal and antioxidant activities were also evaluated. Twenty-three compounds were identified among which germacrene B (50.66%), germacrene D (22.22%) and (E)-caryophyllene (8.99%) were the main compounds. The highest antiproliferative activity was observed against NCI-ADR/RES (TGI = 31.08 μg/ml) and HT-29 (TGI = 32.81 μg/ml) cell lines. It also showed good antileishmanial activity against Leishmania infantum (IC50 = 30.71 μg/ml). On the other hand, the oil exhibited a small effect against Staphylococcus aureus ATCC 6538, S. aureus ATCC 14458 and Escherichia coli ATCC 10799 (MIC = 250 μg/ml), as well as small antioxidant activity (457 μmol TE/g) assessed through ORACFL assay. These results represent the first report regarding chemical composition and bioactivity of G. australis essential oil.

Homoleptic and Heteroleptic Bismuth(III) Thiazole–Thiolates and the Influence of Ring Substitution on Their Antibacterial and Antileishmanial Activity

AbstractTwo new homo‐ and heteroleptic bismuth thiazole‐thiolato complexes derived from 4‐phenylthiazole‐2‐thiol MBT(H) have been synthesised and structurally characterised, [BiPh(MBT)2]2 and [Bi(MBT)3]2. Syntheses were achieved using BiPh3 or Bi(OtBu)3 in protolysis reactions with MBT(H), or by salt metathesis with BiCl3 or BiPhCl2 and the sodium thiolate, [NaMBT]. The complexes were obtained under both standard solvent‐free and solvent‐mediated conditions, and by microwave irradiation. The solid‐state structures of [BiPh(MBT)2]2 and [Bi(MBT)3]2, were determined using single‐crystal X‐ray diffraction, showing them to be dimeric. The bactericidal properties of the complexes against Mycobacterium smegmatis, Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, vancomycin‐resistant Enterococcus (VRE) and Escherichia coli revealed [BiPh(MBT)2]2 to be the most effective against all the bacteria with MIC values of 0.6 μg/mL (0.25 μM) against S. aureus and 0.9 μg/mL (0.27 μM) against E. faecalis. [Bi(MBT)3]2 was less active overall. However, comparisons with the analogous complex [Bi(4‐BrMTD)3], revealed a significant hundred‐fold enhanced activity against S. aureus, MRSA, VRE, and E. faecalis. Both complexes showed little or no toxicity towards mammalian COS‐7 cells at 20 μg/mL. [BiPh(MBT)2]2 also was found to display good antileishmanial activity with an IC50 value of 0.11 μg/mL (0.17 μM), at which concentration the complex was non‐toxic to human fibroblast cells.

Antileishmanial and antimicrobial activity studies of Magnolia grandiflora leaves

As part of a search for novel antileishmanial leads from natural sources we investigated the leaves of Magnolia grandiflora (Magnoliaceae). The primary screening of the methylene chloride extract of M. grandiflora leaves showed activity against Leishmania donovani promastigotes as well as Cryptococcus neoformans. Activity-guided fractionation of this extract led to the isolation of sesquiterpene lactone 4α,5β-epoxy-germacra-1-(10),11-(13)-diene-6α,12-olide (Parthenolide) (1) as the active compound. This compound showed good antileishmanial activity against L. donovani promastigotes, and moderate antifungal activity against C. neoformans. Parthenolide has previously been isolated from several plants including the widely used medicinal plant feverfew (Tanacetum parthenium) and a variety of biological activities including inhibitory activity against the L. amazonensis promastigote have been reported for this compound.

A new fatty alcohol from Terminalia arjuna leaves with antileishmanial activity

A new fatty alcohol (1) together with ten known compounds was isolated from the leaves of Terminalia arjuna Roxb. Their chemical structures were established on the basis of physical, chemical, and spectroscopic methods to be identified as (E)-3,5,7,16 tetramethylheptadeca-2-en-1-ol (1), apigenin, luteolin, vitexin, isovitexin, luteolin-3′-glucuronide, gallic acid, methyl gallate, ellagic acid, stigmasterol, and β-sitosterol-3-O-glucoside. Apigenin, vitexin, and isovitexin were isolated for the first time from this species, while luteolin-3′-glucuronide was isolated for the first time from the genus Terminalia. Compound 1 and its acetate derivative (2) showed good antileishmanial activity with IC50 values of 9.0 and 2.0 μg/mL, respectively.

Evaluation of antileishmanial activity of South Indian medicinal plants against Leishmania donovani

Infections due to protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The aim of this study was to evaluate the in vitro antileishmanial activity of the acetone and methanol leaf extracts of Anisomeles malabarica, flower of Gloriosa superba, leaf of Ocimum basilicum, leaf and seed of Ricinus communis against promastigotes form of Leishmania donovani. Antiparasitic evaluations of different plant crude extracts were performed on 96 well plates at 37°C for 24–48h. Out of the 10 experimental plant extracts tested, the leaf methanol extracts of A. malabarica, and R. communis showed good antileishmanial activity (IC50=126±19.70 and 184±39.33μg/mL), respectively against promastigotes. Effective antileishmanial activity was observed making these plants as good candidates for isolation of antiprotozoal compounds which could serve as new lead structures for drug development.

Synthesis and anti-leishmanial activity of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines containing N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl] moieties

A novel series of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines were synthesized by introducing N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl] moiety as a new functionality on the C-2 amine of thiadiazole ring via click chemistry. The title compounds namely, N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines (3a–n) were characterized by IR, NMR and MS spectra. These compounds were evaluated for their in vitro anti-leishmanial activity against promostigote form of the Leishmania major. Most compounds exhibited good anti-leishmanial activity against the promastigote form of L. major. The most active compound against promostigotes was found to be 4-methylbenzyl analog 3i, which significantly decreases the number of intracellular amastigotes per macrophage, percentage of macrophage infectivity and infectivity index.

Efficient synthesis of 16 aromatic Morita–Baylis–Hillman adducts: Biological evaluation on Leishmania amazonensis and Leishmania chagasi

Sixteen aromatic Morita–Baylis–Hillman adducts (MBHA) 1– 16 were efficiently synthesized in a one step Morita–Baylis–Hillman reaction (MBHR) involving commercial aldehydes with methyl acrylate or acrylonitrile (81–100% yields) without the formation of side products on DABCO catalysis and at low temperature (0 °C). The toxicities of these compounds were assessed against promastigote form of Leishmania amazonensis and Leishmania chagasi. The low synthetic cost of these MBHA, green synthetic protocols, easy one-step synthesis from commercially available and cheap reagents as well as the very good antileishmanial activity obtained for 14 and 16 (IC 50 values of 6.88 μg mL −1 and 11.06 μg mL −1 respectively on L. amazonensis; 9.58 μg mL −1 and 14.34 μg mL −1 respectively on L. chagasi) indicates that these MBHA can be a novel and promising class of anti-parasitic compounds.