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Objectives: To evaluate the in vitro activity of anti-leishmanial drugs against intracellular Leishmania donovani amastigotes in different types of macrophages.Methods: Mouse peritoneal macrophages (PEMs), mouse bone marrow-derived macrophages (BMMF), human peripheral blood monocyte-derived macrophages (PBMF) and differentiated THP-1 cells were infected with L. donovani. Cultures were incubated with sodium stibogluconate, amphotericin B deoxycholate (Fungizone w ), miltefosine or paromomycin sulphate over six concentrations in 3-fold serial dilutions for 5 days. Analysis was based on percentage inhibition of infected macrophages and EC 50 /EC 90 values estimated using sigmoidal curve-fitting. Results:The rank order of drug activity was the same in the different macrophage populations: amphotericin B. miltefosine .sodium stibogluconate. paromomycin. However, significant (P,0.05) differences were observed between populations. Amphotericin B was more active in PEMs and BMMF (EC 50 0.02-0.06 mM) compared with PBMF and differentiated THP-1 cells (EC 50 0.08 -0.40 mM) and miltefosine was more active in PBMF (EC 50 0.16 -0.74 mM) compared with PEMs and BMMF (EC 50 2.60 -7.67 mM). Sodium stibogluconate displayed highest activity in PBMF (EC 50 1.38-1.89 mg Sb v /mL), followed by Conclusions:In vitro activity of anti-leishmanial drugs is host cell dependent. This has implications for: (i) the evaluation of in vitro drug activity; (ii) the evaluation of drug susceptibility of clinical isolates; and (iii) the standardization of anti-leishmanial drug assays.

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Chagas disease, caused by Trypanosoma cruzi parasite, was described thousands of years ago. Currently, it affects millions of people, mostly in Latin America, and there are not suitable drugs for treating it. As an attempt to find appropriate drugs to deal with this problem, we report here on the design, synthesis, and characterization of 82 new compounds. Trypanosomicidal behavior in vitro showed more than 20 outstanding derivatives with anti-Trypanosoma cruzi activity. Furthermore, we studied the nonspecific toxicity against mammalian cells determining their selectivity and also performed mutagenicity studies. Proof of concept, in vivo studies, was conducted with two of the most promising derivatives (77 and 80). They were identified as candidates because they have (i) very simple and cost-effective syntheses; (ii) activity against different stages and strains of the parasite showing excellent in vivo behavior during the acute phase of Chagas disease; and (iii) neither nonspecific toxicity nor mutagenic activity.

In both scid and BALB/c mouse-Leishmania donovani models, hexadecyphosphocholine (miltefosine) and AmBisome had similar levels of activity. In contrast, sodium stibogluconate (Pentostam) was significantly less active against L. donovani in scid mice than in BALB/c mice. The in vitro anti-leishmanial activity of miltefosine was similar in peritoneal macrophages derived from both scid and BALB/c mice, whereas Pentostam and AmBisome were significantly more active in the latter.

This article describes the preparation of a graphene electrode modified with a new conjugate of peptide nanotubes and folic acid for the selective detection of human cervical cancer cells over-expressing folate receptors. The functionalization of peptide nanotubes with folic acid was confirmed by fluorescence microscopy and atomic force microscopy. The peptide nanotube-folic acid modified graphene electrode was characterized by scanning electron microscopy and cyclic voltammetry. The modification of the graphene electrode with peptide nanotube-folic acid led to an increase in the current signal. The human cervical cancer cells were bound to the modified electrode through the folic acid-folate receptor interaction. Cyclic voltammograms in the presence of [Fe(CN)(6)](3-/4-) as a redox species demonstrated that the binding of the folate receptor from human cervical cancer cells to the peptide nanotube-folic acid modified electrode lowered the electron transfer resulting in a decrease in the measured current. A detection limit of 250 human cervical cancer cells per mL was obtained. Control experiments confirmed that the peptide nanotube-folic acid electrode specifically recognized folate receptors. The modified electrode described here opens up new possibilities for future applications in early stage diagnoses of diseases where cells over-express folate receptors, such as in cancer or leishmaniasis disease.