Leishmaniasis is the neglected disease among parasitic diseases with an increasing rate of infections. Recently, numerous studies have been conducted on the Leishmanicidal properties of various essential oils (EOs). In this research, literature have been systematically reviewed, from 20 years ago, and required information have been extracted. Overally, Leishmanicidal effects of ~180 EOs against promastigotes of nine species of Leishmania have been documented. Inhibitory concentrations 50% (IC50) of around 30 EOs were less than 10 μ g. mL-1. EOs of Tetradenia riparia, Nectandra hihua, and Thymus hirtus with IC50s of 0. 01, 0. 20, and 0. 25 μ g. mL-1 against Leishmania amazonensis, Leishmania infantum, and Leishmania major respectively, were identified as the most effective EOs. Furthermore, IC50 of Thymus hirtus on Leishmania infantum was 0. 43 μ g. mL-1. Frequently, substantial differences were found between the observed IC50s of one EO against promastigotes of different species of Leishmania. It can be concluded that the Leishmanicidal activity of EOs is selective. Turning to the results, the combination of EOs for the design of multifunctional drugs can lead to excellent outcomes. Interestingly, the results have been classified by promastigote species, so this would be a valuable benchmark for researchers.

Cutaneous leishmaniasis is caused by protozoa of the genus Leishmania and spread by sandflies. The standard therapy for this ailment is the first-line medication of pentavalent antimonial and the second drug line of pentamidine amphotericin B. All are practiced over the years and exhibit adverse toxicity effects. Herbal product-derived medicine is a promising potential source for treating parasitic diseases. Xanthatin, a xanthanolide sesquiterpene lactone, is isolated from Xanthium strumarium L. treats several ailments in many countries. In the present study, we investigated the Leishmanicidal activity of the xanthatin by using a metabolomicsbased analysis in J774 macrophages and amastigotes phases in Leishmania major. Xanthatin was isolated and identified by NMR spectroscopy. Macrophage toxicity of xanthatin performed by MTT assay. Macrophages infected by the L. major’ s promastigote stationary phase, the infection rate (IR), and multiplication index (MI) were calculated. Axenic amastigotes were treated with xanthatin. Cell quenching and metabolite extraction were performed, and the metabolome profile was analyzed with NMR spectroscopy. Outliers were classified by using multivariate statistical analysis software, and relevant metabolites and pathways were worked out. The xanthatin IC50 rate defined 0. 75 μ g/mL base on macrophages viability and also in-vitro activity of xanthatin on amastigotes showed the best Leishmanicidal activity in IR and MI values of 53% and 62. 5%, respectively. Xanthatin altered amino sugars and nucleotide sugars metabolism, starch and sucrose metabolism, cyanoamino acid, and galactose metabolism. Our finding revealed that the main target of xanthatin is carbon metabolism, which is an essential step for amastigotes virulence.

Background and objectives: Several natural compounds have been identified for the treatment of leishmaniasis. Due to a few safe drugs and the side effects caused by available chemotherapy, some new drugs for treatment of leishmaniasis are requested. The genus Pulicaria (Asteraceae) is represented in the flora of Iran by five species. Phytochemical studies on Pulicaria species have revealed some flavonoids and terpenoids with Leishmanicidal activity. In the present investigation chemical composition and Leishmanicidal activity of Pulicaria gnaphalodes essential oil have been studied.Methods: The essential oil of the aerial parts of the plant was obtained by Clevenger apparatus and was analyzed by GC/MS. Antileishmanil activity was assessed against promastigoes of Leishmania major.Results: The major components from P. gnaphalodes essential oil have been reported to be geraniol, 1, 8-cineole, chrysanthenone, a-pinene, chrystanthenone, a-terpineol and filifolone. The alcohol monoterpenes with contribution of 25.04% constituted the major portion of the essential oil, while hydrocarbon monoterpenes and hydrocarbon sesquiterpenes with contribution of 7.08% and 2.38%, respectively occupied the next rates. In the present experiment the essential oil of P. gnaphalodes progressively inhibited Leishmania major growth in concentrations ranging from 0.125 to 50 mL/mL (parasite culture) in 24 h. The essential oil at 50 mL/mL eliminated the promastigotes at the beginning of treatment. It showed antileishmanial activity in concentration of 1.06 mL/mL and destroyed all parasits in 24 h.Conclusion: Pulicaria gnaphalodes antileishmanial activity, could suggest the species and constituents as possible lead structures for antileishmanial drug discovery.

Background: Paullinia pinnata leaves are employed traditionally for the treatment of various ailments which are of biological origin. Objectives: The aim of this study was to explore cytotoxic, antibacterial, and antileishmanial properties of the leaves of Paullinia pinnata using in vitro models. Methods: Brine shrimp lethality bioassay was used to determine the cytotoxic activity of the methanol leaf extract of Paullinia pinnata. The activity of the extract against the growth of cultured Leishmania major (DESTO) promastigotes was used to investigate the Leishmanicidal activities. The agar well diffusion method was used to investigate the antibacterial activity against Salmonella typhi, Pseudomonas aeruginosa, Shigella flexneri, Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. Results: The methanol leaf extract of P. pinnata had no activity against Artemia salina (brine shrimp) and L. major. It showed a non-significant activity against E. coli and B. subtilis and no activity against P. aeruginosa, S. flexneri, S. typhi, and S. aureus. Conclusion: The methanol leaf extract of P. pinnata did not exhibit any cytotoxic and anti-leishmanial properties. Moreover, the activity against various species of bacteria was not significant.

Purpose: Here, we aim to evaluate the antileishmanial activity of compounds with a benzoxazinoid (BX) skeleton, previously synthesized by our group, against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum promastigotes. Methods: Anti-promastigote activity, as well as cytotoxicity, were determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assays. The selectivity index (SI) for each compound was calculated using a ratio of the cytotoxicity of compounds and the geometric mean (GM) of antileishmanial concentrations to each species tested. The comparisons between groups were carried out using a t test or analysis of variance (one-way ANOVA). A P value of less than 0. 05 was considered significant. Results: All the compounds tested were active, with IC50 falling between 92 ± 6. 19 μ g/mL and 238± 6. 57 μ g/mL for L. braziliensis, and 89 ± 6. 43 μ g/mL and 188 ± 3. 58 μ g/mL against L. infantum. Bex2, Bex3, Pyr1, Pyr2, and Pyr4 were compounds that showed activity similar to the drug Glucantime® , exhibited low cytotoxicity against splenic hamster cells (CC50 raging between >400 and 105. 7± 2. 26 μ g/mL) and had favorable selectivity indices (SI 1. 12 to 3. 96). Conclusion: The analogs in question are promising prototypes for the pharmaceutical development of novel, safer and more effective Leishmanicidal agents.

Background and objectives: Leishmaniasis is caused by the genus of Leishmania and is one of the important health problems worldwide. Serious side effects, the lack of effective vaccines and the emergence of drug resistance are the major weak points of leishmaniasis treatment. The purpose of this study was to evaluate Leishmanicidal effects of Allium giganteum saponin rich fraction, natural compounds with history of antimicrobial properties, on promastigotes and axenic amastigotes of L. major and macrophages cell line J774. Methods: The chloroform-methanol (9: 1) extract of the flowers was fractionated by MPLC using an RP-18 column. The saponin-rich fraction was detected by TLC and H-NMR analyses and evaluated for Leishmanicidal activity on L. major and macrophages cell line J774 using MTT assay at 24, 48 and 72 h of incubation. Results: At concentrations of 75, 100 and 150 μ g/mL, over the time of 24 to 72 h, a significant decrease in the live parasite's rate was observed (p <0. 05). At 200 μ g/mL concentration, all parasites were killed and maximum Leishmanicidal effect was observed. The IC50s for promastigotes and axenic amastigotes were 90. 01 ± 13. 42 μ g/mL and 29. 76± 17. 91 μ g/mL, respectively; the value for the J774 macrophage cell line was 33. 17± 4 μ g/mL. Conclusion: The results of this study showed the significant Leishmanicidal effect of saponin rich fraction from Allium giganteum on promastigote and axenic amastigote of L. major and macrophage cell line in vitro. Complementary in vivo studies for evaluating the effects of the fraction on leishmaniasis in BALB/c mice is recommended.

Four conformationally restricted analogues of pentamidine were prepared. Then, different concentrations (0.039, 0.078, 0.156, 0.312 and 0.625 mg/mL) of each compound and two positive controls (amphotericin B and pentamidine, 0.625 mg/mL), one negative control (culture medium) and one solvent control (DMSO) were prepared and placed in 24-well plates containing 50000 parasite per well. Promastigotes of Leishmania major were incubated over a period of 2 days at 25oC; subsequently, percent of viable parasite in each well determined spectrophotometrically using MTT assay. The average EC50 for compounds 4a,b and 8a,b in DMSO was 0.098, 0.410, 0.150, 0.720 mg/mL, respectively. The average EC50 for positive controls pentamidine and amphotericin B was found to be 0.062 and 0.026 mg/mL. The control solvent had no significant effect on L. major promastigotes,. All compounds had significant effect compared to DMSO and were less potent than positive controls.

Background: Leishmania is a trypanosomatid protozoan which is transmitted by the female Phlebotomus sand fly. Leishmaniasis is prevalent in four continents and is considered to be endemic in 88 countries, 72 of which are developing countries. It is estimated that it’s global prevalence and incidence is 12 millions and 500 thousands respectively. The recommended drugs used for the treatment of this disease are mainly ineffective, toxic and exhibit many side effects. Based on some studies, tea tree oil that is a yellow color liquid with spicy odor exhibit antibacterial and antifungal activity, so, we evaluated it’s anti-leishmanial effect.Materials and Methods: Tea tree oil was purchased from Dr Jahangiri pharmaceutical company and it’s various concentrations (mg/ml800, mg/ml400, mg/ml200, mg/ml100) were prepared in 1ml volume of TSB solvent in 15ml test tubes, then 9ml of RPMI-1640medium and 1´106 promastigotes was added to each tube, as a final volume of 10 ml. These tubes were incubated at 23o c for 72 hours and number of parasites in the first 6 hours once every hour and after that every 24 hours were counted by hemocytometer.Results: Lethal dose of tea tree oil for 50% of promastigotes (IC50) is 337 mg/ml, while the 800 mg/ml of this extract can killed 95% of the parasites after 24 hours of incubation, and it’s lower concentrations of this extract showed dose-dependent Leishmanicidal activity. Glucantime as positive control drug at concentration of 300 mg/ml killed all the promastigotes, while the number of promastigotes in negative control tubes was increase during the incubation period.Conclusion: Anti-Leishmanial activity of tea tree oil with IC50 of 337 mg/ml and 95% lethality of 800 mg/ml is promising and further study for analyse the active ingredients of this oil and evaluation of it’s anti-leishmanial effect, particularly in laboratory animal is recommended.

Leishmaniasis and malaria are serious public health problems in tropical and sub-tropical regions worldwide. Development of drug-resistant strains has disrupted efforts to control the spread of these diseases in the world. The conventional antiparasitic chemotherapy still suffers from side effects and drug resistance. Therefore, the development of novel antimalarial and Leishmanicidal drugs remains a critical topic to combat against these diseases. Five-membered heterocyclic systems have possessed antiparasitic activity such as thiadiazole scaffold which is a prevalent and an important heterocyclic ring. For this purpose, the authors introduce a series of synthetic thiadiazole derivatives with antileishamanial activity. Also, the authors searched a number of sources and articles to find thiadiazole derivatives with antileishamnial and antimalarial activity. Then all of the findings were reviewed. 5-nitroheteroaryl-1, 3, 4-Thiadiazole derivatives with different substituents at position 2 of the thiadiazole ring (8, 10-11) presented the best antileishmanial activity with low toxicity compared with reference drug. Also, 1, 3, 4-thiadiazole-2-sulfonamide derivative (18) showed excellent inhibitory activity against pfCA as a special enzyme in Plasmodium falciparum. Thiadiazole scaffold has the suitable physicochemical and pharmacokinetic properties and still stays as a therapeutic target for the development of a novel lead in the medicinal chemistry. Therefore, the current review provides a brief summary of medicinal chemistry of thiadiazole ring and introduces novel leads possessing this nucleus with antimalarial and antileishmanial activities.