Pentamidine is an effective trypanocidal drug used against stage 1 Human African Trypanosomiasis (HAT). At the blood-brain barrier (BBB), it accumulates inside the endothelial cells but has limited entry into the brain. This study examined transporters involved in pentamidine transport at the human and mouse BBB using hCMEC/D3 and bEnd.3 cell lines, respectively. Results revealed that both cell...

Treatment of many infectious diseases is under threat from drug resistance. Understanding the mechanisms of resistance is as high a priority as the development of new drugs. We have investigated the basis for cross-resistance between the diamidine and melaminophenyl arsenical classes of drugs in African trypanosomes. We induced high levels of pentamidine resistance in a line without the tbat1 g...

The use of aerosolized pentamidine was investigated in ten patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) who had previous or concurrent severe adverse reactions or contraindications to trimethoprim-sulfamethoxazole or parenteral pentamidine. A dose of 600 mg pentamidine in 6 ml sterile water, aerosolized in a small-particle producing jet ne...

The efficacy and tolerance of pentamidine aerosol were evaluated in the prophylaxis and therapy of murine Pneumocystis carinii pneumonia. P. carinii pneumonia was induced in rats by corticosteroid immunosuppression. Pentamidine was administered three times weekly via a Bird micronebulizer. The actual amount of pentamidine inhaled was estimated by monitoring the ventilation of the rats during th...

The antimicrobial agent pentamidine inhibits the self-splicing of the group I intron Ca.LSU from the transcripts of the 26S rRNA gene of Candida albicans, but the mechanism of pentamidine inhibition is not clear. We show that preincubation of the ribozyme with pentamidine enhances the inhibitory effect of the drug and alters the folding of the ribozyme in a pattern varying with drug concentrati...

During the first stage of human African trypanosomiasis (HAT), Trypanosoma brucei gambiense is found mainly in the blood, and pentamidine treatment is used. Pentamidine is predominantly ineffective once the parasites have invaded the central nervous system (CNS). This lack of efficacy is thought to be due to the inability of pentamidine to cross the blood-brain barrier, although this has never ...

Acute kidney injury (AKI) is a recognised complication of intravenous pentamidine therapy. A direct nephrotoxic effect leading to acute tubular necrosis has been postulated. We report a case of severe renal allograft dysfunction due to nebulised pentamidine. The patient presented with repeated episodes of AKI without obvious cause and acute tubular necrosis only on renal histology. Nebulised pe...

Four conformationally restricted analogues of pentamidine were prepared. Then, different concentrations (0.039, 0.078, 0.156, 0.312 and 0.625 mg/mL) of each compound and two positive controls (amphotericin B and pentamidine, 0.625 mg/mL), one negative control (culture medium) and one solvent control (DMSO) were prepared and placed in 24-well plates containing 50000 parasite per well. Promastigo...

The chemotherapeutic arsenal against human African trypanosomiasis, sleeping sickness, is limited and can cause severe, often fatal, side effects. One of the classic and most widely used drugs is pentamidine, an aromatic diamidine compound introduced in the 1940s. Recently, a genome-wide loss-of-function screen and a subsequently generated trypanosome knockout strain revealed a specific aquagly...

Drug resistance by overexpression of ATP-binding cassette (ABC) transporters is an impediment in the treatment of leishmaniasis. Flavonoids are known to reverse multidrug resistance (MDR) in Leishmania and mammalian cancers by inhibiting ABC transporters. Here, we found that synthetic flavonoid dimers with three (compound 9c) or four (compound 9d) ethylene glycol units exhibited a significantly...