The uptake of the trypanocidal drug suramin in combination with low-density lipoproteins by Trypanosoma brucei and its possible mode of action

Distribution of Suramin, an Antitrypanosomal Drug, across the Blood-Brain and Blood-Cerebrospinal Fluid Interfaces in Wild-Type and P-Glycoprotein Transporter-Deficient Mice

“…[ 14 C]sucrose, a nonmetabolizable carbohydrate, is excluded from the brain, as it does not cross the BBB (25) (31), and this is possibly indirectly linked to LDL (40). In addition, the caveola system is important in [ 3 H]suramin uptake by the human dermal microvascular endothelium (14).…”

“…Interestingly, suramin is taken up by human dermal microvascular endothelial (HMEC-1) cells by an active process involving the caveola system (14). In addition, suramin is thought to slowly enter the parasite by receptor-mediated endocytosis (31), which is possibly linked to host low-density lipoprotein (LDL) endocytosis (40). Furthermore, LDL receptors are expressed at the BBB (29) and are believed to be involved in the transcytosis of LDL from the blood to the brain (11).…”

Dithiol Proteins as Guardians of the Intracellular Redox Milieu in Parasites: Old and New Drug Targets in Trypanosomes and Malaria‐Causing Plasmodia

“…After pre-and postdoctoral studies on single-turnover kinetics of enzyme catalysis with Professor C. H. Williams and Professor V. Massey at the University of Michigan in Ann Arbor, he returned to the BZH to work on the design and synthesis of disulfide reductase inhibitors. [3,4] ; but see also reference [5] unknown; the sulfonated naphthylamine interacts electrostatically with many enzymes [6,7] pentamidine (1937) multiple transporters [3,8,9] , for example, the P2 adenine/adenosine transporter the aromatic diamidine is enriched in the parasite to millimolar concentrations; thus there are many targets (proteins, lipids, minor groove of DNA [10][11][12] ) melarsoprol (melB)…”

Suramin inhibits macrophage activation by human group IIA phospholipase A2, but does not affect bactericidal activity of the enzyme

“…In addition, the strong polyanionic nature of suramin facilitates a stable interaction with cationic surfaces of a wide range of basic proteins [51,52]. The strong binding to plasma proteins at physiological pH results in the sequestration of approximately 85 % of the total suramin at therapeutic concentrations, typically around 1 mM [53]. This implies a free plasma concentration of around 150 µM, which is similar to the levels at which the inhibitory effects against hsPLA 2 GIIA are observed in the present study.…”