Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. WHO estimates that the disease results in 2 million new cases a year, threatens 350 million people in 88 countries and that there are 12 million people currently infected worldwide. Current treatment is based on chemotherapy, which relies on a handful of drugs with serious limitations such as high cost, toxicity, difficult route of administration and lack of efficacy in endemic areas. Pentavalent antimonials have been the mainstay of antileishmanial therapy for over 70 years with second line drugs, Amphotericin B and Pentamidine, used in case of antimonial failure. Since the introduction of miltefosine at the beginning of this century, no new antileishmanial compounds have been approved for human treatment. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. However, to date no such vaccine is available despite substantial efforts by many laboratories. The development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. This review outlines the current status of vaccine development and looks at the currently available chemotherapy as well as examples of drugs in development and different approaches to antileishmanial drug discovery and identification of novel antiparasitic compounds.

Two new three-dimensional porous Cd(II)-based metal–organic frameworks, [Cd₂(oba)₂(4-bpdb)₂]_n·(DMF)_x (TMU-8) and [Cd(oba)(4,4′-bipy)]_n·(DMF)_y (TMU-9), have been synthesized via mechanosynthesis by using nonlinear dicarboxylate and linear N-donor ligands and then characterized by single-crystal X-ray crystallography. The effect of using different N-donor ligands 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene (4-bpdb) and 4,4′-bipyridine (4,4′-bipy) as pillars on the final structure has been studied. Also, the removal efficiency and order reaction kinetics of these MOFs in the presence of Congo red were investigated.

The neutral germanium(I) dimers, [{Ge(Piso)}₂] and [{Ge(Giso)}₂], Piso = [(ArN)₂CBu^t]⁻, Giso = [(ArN)₂CNPrⁱ ₂]⁻, Ar = C₆H₃Prⁱ ₂-2,6, which are stabilised by bulky amidinate and guanidinate ligands respectively, have been prepared by reduction of the corresponding germanium(II) chlorides, [Ge(Piso)Cl] and [Ge(Giso)Cl]; theoretical studies suggest that the Ge–Ge bonds of [{Ge(Piso)}₂] and [{Ge(Giso)}₂] are associated with their HOMOs, whilst their LUMOs have substantial Ge–Ge π-bonding character.

Background— Generation of the second-messenger molecule ceramide by stimulated sphingomyelinase activity has been implicated in the inflammatory processes contributing to the pathogenesis of atherosclerosis. However, reports of stimulatory effects of ceramide on endothelial NO production in animal models suggest antiatherosclerotic effects of the molecule. Therefore, we investigated long-term effects of ceramide on NO generation in human endothelial cells. Methods and Results— In human umbilical vein endothelial cells (HUVECs) and in HUVEC-derived EA.hy 926 endothelial cells, C6-ceramide ( N -hexanoyl- d -erythro-sphingosine) reduced the generation of bioactive NO (RFL-6 reporter-cell assay). At the same time, the signaling molecule increased endothelial NO synthase (eNOS) mRNA (RNase protection assay) and protein expression (Western blot). C6-ceramide stimulated eNOS transcription by a signaling mechanism involving protein phosphatase PP2A but did not modify the stability of the eNOS mRNA. Endothelial generation of reactive oxygen species (ROS) was increased by C6-ceramide [5-(and-6)-chloromethyl-2′, 7′-dichlorodihydrofluorescein diacetate (CM-H ₂ DCFDA) oxidation-based fluorescence assay], and this effect was partially reversed by the NOS inhibitor N ^G -nitro- l -arginine methyl ester (L-NAME). On the other hand, (6 R )-5,6,7,8-tetrahydro- l -biopterin (BH ₄ ) normalized in part the ceramide-induced reduction in bioactive NO. Conclusions— Ceramide produces oxidative stress in human endothelial cells, thereby reducing bioactive NO. The partial reversal of this reduction by BH ₄ and the diminution of ROS generation by L-NAME suggest that ceramide promotes NADPH oxidase activity of eNOS, leading to ROS formation at the expense of NO synthesis. The ceramide-induced upregulation of eNOS gene transcription can be considered an ineffective compensatory mechanism. The decreased bioavailability of NO is likely to favor a proatherogenic role of ceramide.