Recent scientific evidence indicates that distinct patterns of susceptibility in BALB/c mice to Leishmania major infection are attributable to the differential expansion of distinct CD4+ T-cell subsets and their cytokines production. Production of the Th1 cytokine IFN-g is associated with resistance, whereas production of the Th2 cytokines IL-4 and IL-10 are associated with extreme susceptibility. The major host immune defense mechanism against Leishmania is activation of macrophages by INF-? derived from T cells. The inability of susceptible hosts to mount the immune response necessary to activate macrophage and destroy the parasites may be due to the parasite-specific proteins that are able to suppress the immune system. In the present study, we have semi-purified the excreted antigens of Leishmania major PROMASTIGOTE and amastigote by column chromatography. The isolated fraction showed a potent immunosuppressive activity on normal BALB/c mice lymphocytes stimulated with mitogens. Fifteen microgram of the isolated fraction caused 81% suppression of lymphocyte proliferation. These data may suggest that the parasite by secreting immunosuppressive factor down regulate the immune system and as a result survive in the body.

Background: Today, most patients with cutaneous leishmaniasis are treated with drugs such as glucantime; however, severe drug resistance to these drugs is found, in addition to recurrence, extensive drug complications, and secondary infections in many patients. Objectives: Therefore, due to the lack of sufficient information on this subject, this study was undertaken for the first time to investigate the antimicrobial activity of multifunctional lactoferrin as one of the most important bioactive compounds on amastigotes and PROMASTIGOTEs forms of Leishmania major in vitro. Methods: In this study, six concentrations of lactoferrin (2. 5, 5, 10, 20, 40, and 80  g/mL) were added to parasite cultures at specified times. The MTT was done. Leishmania major PROMASTIGOTEs were incorporated to J774 cells and then incubated for 72 hours. The results were compared with the results of glucantime, as a standard. In the end, flow cytometry was performed to investigate apoptosis. Results: After 24, 48, and 72 hours of incubation in the presence of various concentrations of lactoferrin, the number of amastigotes and PROMASTIGOTE parasites increased over time without any significant difference compared to the control group (P > 0. 05), but it was significant compared to glucantime at the 80  g/mL concentration (P < 0. 05). Besides, lactoferrin showed very low toxicity effects on macrophages and stimulated the growth of both forms of L. major parasite. Conclusions: Our findings indicated that lactoferrin could not induce early and late apoptosis in both forms of L. major.

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: Since the discovery of hybridoma cells, the uses of monoclonal antibodies (mAbs) are in vogue. Such antibodies with single isotype have high specificity. The developments in the field of cell culture and technology have led to the production of improved qualities of mAbs. In general, mAbs are important reagents used in biomedical research, as well as in targeted drug delivery systems. Objective: The aim of this study was to apply different strategies to produce mAbs against proamastigote Leishmania infantum strain in Iran. Materials and Methods: At first, standard strains were cultured and antigens of L. infantum were obtained. Afterward, BALB/c mice were immunized and antibody titers were determined. For hybridoma cell formation, isolated lymphocyte cells from spleen of immunized mice and myeloma cells were fused at the ratio of 10: 1 in the presence of polyethylene glycol and followed by limiting dilution method for the isolation of monoclones. Results: More than 20 positive monoclones were hybridoma, from which 3 clones had optical density over 1. 5. We named these clones as 5D2 FVI6, 3G2 FV7, and 3G2 FV5 which were selected for limiting dilution. From these hybrids, anti-PROMASTIGOTEs L. infantum mAbs were obtained. The results of isotype determination showed IgG2b sub-class (and not IgG1, IgG2a and IgA) in 5D2 FV and 3G2 FVI monoclones. Conclusion: This study produced mAbs against PROMASTIGOTEs of Iranian strain of L. infantum for the first time. These antibodies have reactivity against Iranian strain of PROMASTIGOTEs L. infantum and can be used in the diagnosis of visceral leishmaniasis.

In this study, a series of novel compounds based on 5-(5-nitrothiophene2--yl)-1, 3, 4-thiadiazole possessing (het) aryl thio pendant at C-2 position of thiadiazole ring is developed and evaluated as antileishmanial agents using MTT colorimetric assay. 10 New compounds containing aryl and heteroaryl derivatives, started from thiophene-2-carbaldehyde in five steps, were synthesized in good to excellent yields and characterized by 1H-NMR, 13C-NMR, and IR spectroscopy. Through the compounds 6a-j, methylimidazole containing derivative 6e was recognized as the most active compound against L. major PROMASTIGOTEs exhibiting IC50 values of 11. 2μ g/mL and 7. 1μ g/mL after 24 and 48 h, respectively. This compound is > 4 fold more effective than Glucantime as a standard drug (IC50 = 50 μ g/mL after 24 h and 25 μ g/mL after 48 h).