Metronidazole Interaction with Cu and Zn: Speciation Study in Aqueous Solution and Biological Activity Evaluation.

Metronidazole (2-methyl-5-nitro-1-imidazole-1-ethanol, MNZ) is a well-known and widely used drug for its excellent activity against various anaerobic bacteria and protozoa. The purpose of this study is to elucidate the ability of MNZ to form metal complexes with Cu and Zn and to demonstrate that complexation increases its bioactivity profile against different pathogenic microorganisms. The interaction of MNZ with Cu and Zn was investigated in NaCl aqueous solution under different conditions of temperature (15, 25, and 37 °C) and ionic strength (0.

Design and Synthesis of 1,3-Diarylpyrazoles and Investigation of Their Cytotoxicity and Antiparasitic Profile.

Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound /HIT 8. We previously identified this molecule as a 'hit' during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core at its 1-, 3-, and 4-position.

Novel quinoline derivatives with broad-spectrum antiprotozoal activities.

Several quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized and evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness (Trypanosoma brucei rhodesiense), nagana (Trypanosoma brucei brucei), Chagas disease (Trypanosoma cruzi), and leishmaniasis (Leishmania infantum). Several of the compounds demonstrated significant antiprotozoal activity. Specifically, compounds 2c, 2d, and 4i displayed submicromolar activity against T.

Hit-to-lead optimization of a 2-aminobenzimidazole series as new candidates for chagas disease.

Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Because current treatments present several limitations, including long duration, variable efficacy and serious side effects, there is an urgent need to explore new antitrypanosomal drugs. The present study describes the hit-to-lead optimization of a 2-aminobenzimidazole hit 1 identified through in vitro phenotypic screening of a chemical library against intracellular Trypanosoma cruzi amastigotes, which focused on optimizing potency, selectivity, microsomal stability and lipophilicity.

Antiplasmodial activity of constituents and their metabolites after in vitro gastrointestinal biotransformation of a Nauclea pobeguinii extract.

Nauclea pobeguinii is traditionally used for treatment of malaria. Previous studies on the plant extract and strictosamide, the putative active constituent, showed a profound in vivo activity of the extract but no in vitro activity of strictosamide. This might indicate that one or more compounds present in the extract, most likely alkaloids, act as prodrugs undergoing biotransformation after oral administration resulting in the active compounds.

Preexisting antiadenoviral immunity and regional myocardial gene transfer: modulation by nitric oxide.

The utility of adenoviral vectors, currently used in cardiovascular gene transfer protocols, is limited by the brevity of transgene expression and by antiadenoviral immune responses. The effect of preexisting antiadenoviral immunity on intracardiac gene transfer or its modulation by nitric oxide is unknown. Adenoviral vectors, expressing the firefly luciferase gene (AdLuc) or the human nitric oxide synthase 3 (NOS3) gene (AdNOS3), were infused into the great cardiac vein of naive pigs or immunized pigs.

Overexpression of a constitutively active protein kinase G mutant reduces neointima formation and in-stent restenosis.

Background: Neointima formation after arterial injury is associated with reduced vascular cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG), a major cGMP effector in vascular smooth muscle. We tested the effect of PKG overexpression on the neointimal response to vascular injury. Methods and Results- Infection of cultured rat aortic smooth muscle cells (RASMCs) with an adenoviral vector specifying a cGMP-independent, constitutively active PKG mutant (AdPKGcat) reduced serum-induced migration by 33% and increased serum-deprivation-induced apoptosis 2-fold (P<0.