Track topics on Twitter Track topics that are important to you
We report the discovery of new 4-hydroxyphenyl phosphonium salt derivatives active in the submicromolar range (EC50 from 0.04 to 0.28 µM, SI > 10) against the protozoan parasite Leishmania donovani. The pharmacokinetics and in vivo oral efficacy of compound 1 [(16-(2,4-dihydroxyphenyl)-16-oxohexadecyl)triphenylphosphonium bromide] in a mouse model of visceral leishmaniasis were established. Compound 1 reduced the parasite load in spleen (98.9%) and liver (95.3%) of infected mice after an oral dosage of 4 daily doses of 1.5 mg/kg. Mode of action studies showed that compound 1 diffuses across the plasma membrane, as designed, and targets the mitochondrion of Leishmania parasites. Disruption of the energetic metabolism, with a decrease of intracellular ATP levels as well as mitochondrial depolarization together with a significant ROS production, contributes to the leishmanicidal effect of 1. Importantly, this compound was equally effective against antimonials and miltefosine-resistant clinical isolates of Leishmania infantum indicating its potential as antileishmanial lead.
This article was published in the following journal.
Name: Journal of medicinal chemistry
A readily available quaternary phosphonium salt containing a trifluoroacetonyl group and a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BAr) counterion was demonstrated to be a highly active Brøns...
A pyridine-pyridine coupling reaction has been developed between pyridyl phosphonium salts and cyanopyridines using B2pin2 as an electron-transfer reagent. Complete regio- and cross-selectivity are ob...
A series of new lawsone Mannich bases derived from salicylaldehydes or nitrofurfural were prepared and tested for their activities against Leishmania major, Toxoplasma gondii, and Trypanosoma brucei b...
Alkylated pyridines are common in pharmaceuticals, and metal catalysis is frequently used to prepare this motif via Csp-Csp coupling processes. We present a cobalt-catalyzed coupling reaction between ...
The first enantioselective aza-Darzens reaction of cyclic imines with α-halogenated ketones was realized under mild reaction conditions, by using amino acid-derived bifunctional phosphonium salts as ...
ADDERALL XR (Mixed Salts of a Single-Entity Amphetamine) and STRATTERA ( Atomoxetine Hydrochloride) Compared to Placebo on Simulated Driving Safety and Performance and Cognitive Functioning in Adults With ADHD
Evaluate the efficacy of treatment with ADDERALL XR and STRATTERA compared to placebo on simulated driving safety and performance of young adults with ADHD as measured by Driving Safety Sc...
The purpose of this prospective clinical trial is to document the performance and clinical outcomes of Biomet Discovery Elbow.
Active discopathies or MODIC 1, are a diagnostic entity discovery with the contribution of MRI in which the first cases were described by Dr. Michael MODIC in 1988. It is characterized by ...
Chemotherapy with platinum salts is very emetic. The aim of this study is to evaluate the benefits of foot reflexology in nausea and vomiting induced by platinum salts-based chemotherapy i...
This is a new gene discovery program for individuals with PCD who do not have a specific genetic etiology identified. Research procedures involve a single blood draw from the affected indi...
Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455)
A chemical reagent that reacts with and modifies chemically the tryptophan portion of protein molecules. Used for 'active site' enzyme studies and other protein studies. Sometimes referred to as Koshland's reagent.
Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are CASE-CONTROL STUDIES; COHORT STUDIES; and CROSS-SECTIONAL STUDIES.
Works about research studies that evaluate interventions or exposures on biomedical or health-related outcomes. The two main types of clinical studies are interventional studies (clinical trials) and observational studies.
Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Tropical Medicine is the study of diseases more commonly found in tropical regions than elsewhere. Examples of these diseases are malaria, yellow fever, Chagas disease, Dengue, Helminths, African trypanosomiasis, Leishmaniasis, Leprosy, Lymphatic filaria...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...