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Chemistry & Biodiversity Oct 2005We have determined the cytotoxic properties of pentamidine isethionate (2) towards the promastigotes of the protozoan parasite Leishmania infantum. The leishmanicidal...
We have determined the cytotoxic properties of pentamidine isethionate (2) towards the promastigotes of the protozoan parasite Leishmania infantum. The leishmanicidal activity of 2 was 60 times higher after 72 h of incubation than that of cisplatin (4). The pentamidine salt 2 induced a higher amount of programmed cell death (PCD) than cisplatin, which is associated with inhibition of DNA synthesis and cell-cycle arrest in the G2/M phase. Circular dichroism (CD) data indicate that binding of 2 to calf-thymus DNA (CT-DNA) induces conformational changes in the DNA double helix, consistent with a B-->A transition. Moreover, the interaction of 2 with ubiquitin led to a 6% increase in the beta-sheet content of the protein as observed by CD spectroscopy. Fluorescence-spectroscopy studies agreed with the CD data, showing that the pentamidine portion of 2 induces a significant decrease in the fluorescence of the Ub residues Phe4 and Phe45 located on the beta-cluster of the molecule, but not of Tyr59 on the alpha-cluster. These data indicate that pentamidine specifically modifies the beta-cluster, i.e., the 'basic face' of ubiquitin. Our results suggest that the biochemical mechanism of action of pentamidine may be a consequence of its dual binding to DNA and proteins.
Topics: Amino Acid Sequence; Animals; Antiprotozoal Agents; Apoptosis; Leishmania infantum; Models, Molecular; Molecular Structure; Pentamidine; Protein Binding; Ubiquitin
PubMed: 17191940
DOI: 10.1002/cbdv.200590111 -
Transactions of the Royal Society of... 1992
Topics: Humans; Pentamidine; Trypanosomiasis, African
PubMed: 1440839
DOI: 10.1016/0035-9203(92)90274-g -
Lancet (London, England) May 1988
Topics: Amidines; Humans; Pentamidine; Pneumonia, Pneumocystis
PubMed: 2896902
DOI: 10.1016/s0140-6736(88)91881-8 -
Lancet (London, England) Oct 1989
Topics: Humans; Hypoglycemia; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis
PubMed: 2571784
DOI: 10.1016/s0140-6736(89)93026-2 -
Lancet (London, England) Mar 1988
Topics: Aerosols; Amidines; Homosexuality; Humans; Male; Pentamidine; Pneumonia, Pneumocystis
PubMed: 2894573
DOI: 10.1016/s0140-6736(88)91441-9 -
Lancet (London, England) Nov 1987
Topics: Aerosols; Amidines; Bronchial Spasm; Humans; Pentamidine
PubMed: 2890038
DOI: 10.1016/s0140-6736(87)91568-6 -
National Cancer Institute Monograph Oct 1976Pentamidine is an aromatic diamidino compound synthesized originally for the therapy of trypanosomiasis. The pharmacologic effects of pentamidine vary, depending on its...
Pentamidine is an aromatic diamidino compound synthesized originally for the therapy of trypanosomiasis. The pharmacologic effects of pentamidine vary, depending on its route of administration. In animals, the dominant effects have been a precipitous, transitory drop in blood pressure after injection and renal toxicity following repeated administration. To avoid the possibility of immediate toxic reactions associated with iv administration, we now usually give the drug im to humans. Further interest in pentamidine has been stimulated by its usefulness in the treatment of interstitial pneumonia caused by Pneumocystis carinii. In some patients receiving antineoplastic or immunosuppressive therapy who have superimposed P. carinii pneumonia, pentamidine may cause serious renal toxicity. Distribution and excretion studies in animals indicate pentamidine is deposited in tissues, with the greatest concentration in the kidneys, and gradually eliminated over a prolonged period. The mechanism of action of pentamidine against P. carinii or the means whereby fixation in tissues and subsequent toxicity occur have not been elucidated. Recent investigations to help clarify these points indicate that pentamidine inhibits dihydrofolate reductase in all tissues studied both in vitro and in vivo. In addition, pentamidine interacts and forms water-insoluble products with specific nucleotides and nucleic acids.
Topics: Amidines; Animals; Blood Pressure; Feces; Folic Acid Antagonists; Kidney; Liver; Mice; Nucleic Acids; Pentamidine
PubMed: 1018718
DOI: No ID Found -
The Journal of the Association of... 1991
Topics: Acquired Immunodeficiency Syndrome; Administration, Inhalation; Humans; Pentamidine; Pneumonia, Pneumocystis
PubMed: 1873532
DOI: No ID Found -
Artificial Cells, Nanomedicine, and... Dec 2019Nanoparticles (NPs) have gained importance in addressing drug delivery challenges across biological barriers. Here, we reformulated pentamidine, a drug used to treat... (Comparative Study)
Comparative Study
Nanoparticles (NPs) have gained importance in addressing drug delivery challenges across biological barriers. Here, we reformulated pentamidine, a drug used to treat Human African Trypanosomiasis (HAT) in polymer based nanoparticles and liposomes and compared their capability to enhance pentamidine penetration across blood brain barrier (BBB). Size, polydispersity index, zeta potential, morphology, pentamidine loading and drug release profiles were determined by various methods. Cytotoxicity was tested against the immortalized mouse brain endothelioma cells over 96 h. Moreover, cells monolayer integrity and transportation ability were examined for 24 h. Pentamidine-loaded polycaprolactone (PCL) nanoparticles had a mean size of 267.58, PDI of 0.25 and zeta potential of -28.1 mV and pentamidine-loaded liposomes had a mean size of 119.61 nm, PDI of 0.25 and zeta potential 11.78. Pentamidine loading was 0.16 µg/mg (w/w) and 0.17 µg/mg (w/w) in PCL NPs and liposomes respectively. PCL nanoparticles and liposomes released 12.13% and 22.21% of pentamidine respectively after 24 h. Liposomes transported 87% of the dose, PCL NPs 66% of the dose and free pentamidine penetration was 63% of the dose. These results suggest that liposomes are comparatively promising nanocarriers for transportation of pentamidine across BBB.
Topics: Animals; Blood-Brain Barrier; Cell Line; Drug Carriers; Drug Liberation; Liposomes; Mice; Nanoparticles; Pentamidine; Phosphatidylcholines; Polyesters
PubMed: 31007068
DOI: 10.1080/21691401.2019.1596923 -
Revista Espanola de Cardiologia Dec 1996Systemic side effects caused by parenteral pentamidine are frequent. They can be severe and life-threatening. Intravenous pentamidine may cause a variety of... (Review)
Review
Systemic side effects caused by parenteral pentamidine are frequent. They can be severe and life-threatening. Intravenous pentamidine may cause a variety of abnormalities in the cardiac conduction system as tachyarrhythmias, hypotension and/or non-specific ECG changes (a long corrected QT interval). There is only one case of previously reported bradyarrhythmias in an HIV-infected patient. We present a new adverse effect associated with intravenous pentamidine therapy, and to the best of our knowledge, this is the first reported case of sinus bradycardia in a patient who is not HIV-infected.
Topics: Bradycardia; Chronic Disease; Female; HIV Seronegativity; Humans; Injections, Intravenous; Lupus Erythematosus, Systemic; Middle Aged; Pentamidine; Pneumonia, Pneumocystis
PubMed: 9026843
DOI: No ID Found