Dicationic diamidines, such as diminazene and pentamidine, are well-studied chemotherapeutic agents with significant activity against parasitic diseases. The in vitro activities of novel diamidine compounds against the Babesia divergens strains 1903B and 4201 were investigated. The most potent compound, a diphenyl furan, had a 50% inhibitory concentration (IC(50)) of 1.5 ng/ml. In a murine mode...

Different sugar-grafted liposomes were prepared and tested against experimental leishmaniasis in vivo using the classical drug pentamidine isethionate and its methoxy derivative. Both the drugs, when encapsulated in sugar-grafted liposomes were found to be more potent in comparison to normal liposome-encapsulated drug or to the free drug. Moreover, the mannose-grafted liposomes were adjudged to...

Aquaglyceroporin-2 is a known determinant of melarsoprol-pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2-AQP3 tandem locus was described from melarsoprol-pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroducti...

Cryptosporidicidal effects of two polyether ionophores (maduramicin and alborixin), a fluorinated 4-quinolone (enrofloxacin), and three analogs of pentamidine were evaluated in a suckling mouse bioassay. Treatment with all compounds except enrofloxacin and one of the pentamidine analogs [1,3-di(4-imidazolinophenoxy)propane] resulted in significant (P less than 0.05) reductions in oocyst excretion.

The Saccharomyces cerevisiae PNT1 gene was isolated and characterized. When present in high copy number in S. cerevisiae, PNT1 confers resistance to the anti-Pneumocystis carinii drug pentamidine. The PNT1 gene encodes a previously uncharacterized polypeptide of 409 amino acids. The predicted gene product is a very basic (pI 9.9) polypeptide with one potential membrane-associated region. PNT1 i...

The activity of several diarylheptanoid derivatives (curcuminoids) was previously evaluated against Leishmania amazonensis promastigotes and among them the most active compound was the [1-(4-methoxy-phenyl)-7-(3,4-methoxy-4-hydroxy-phenyl)-1,6-heptadien-3, 5-dione]. This derivative was chosen to be assayed in vivo in a treatment trial. For these experiments, the curcuminoid compound was used in...

The Respigard II nebulizer system is the approved method to deliver pentamidine aerosols in the USA. Although continuous operation of the nebulizer until dryness is a designated regimen, the actual pentamidine dose delivered under the operating condition has not been thoroughly studied. Pentamidine solutions (300 mg in 6 mL water) were nebulized continuously with the Respigard II nebulizer syst...

Aerosolised pentamidine 300 mg in 5 or 6 ml solution was administered via 8 different nebuliser systems to 12 patients with acquired immunodeficiency syndrome. Using 99mTc human serum albumin as an indirect marker for pentamidine, pulmonary, extrapulmonary (gastric and oropharyngeal) and alveolar deposition of pentamidine were measured using a gamma camera. Side effects (visual analogue scales)...

DNA repair mechanisms are crucial for the maintenance of genomic stability and are emerging as potential therapeutic targets for cancer. In this study, we report that the endo-exonuclease, a protein involved in the recombination repair process of the DNA double-stranded break pathway, is overexpressed in a variety of cancer cells and could represent an effective target for developing anticancer...

The antiparasitic activity of aromatic diamidine drugs, pentamidine and furamidine, depends on their entry into the pathogenic protozoa via membrane transporters. However, no such diamidine transporter has been identified in mammalian cells. The goal of this study is to investigate whether these dicationic drugs are substrates for human organic cation transporters (hOCTs, solute carrier family ...