Glucosylated Deferiprone and Its Brain Uptake: Implications for Developing Glucosylated Hydroxypyridinone Analogues Intended to Cross the Blood−Brain Barrier

Abstract

This report presents that Deferiprone, the only clinically used 3-hydroxypyridin-4-one (HPO), is able to penetrate the blood-brain barrier (BBB) in guinea pigs, whereas its glucosylated analogue is unable to do so. This finding is contrary to published information suggesting that the glucosylation of HPOs is a viable means of enhancing the brain uptake of this group of compounds.

Synthesis and Antiviral Bioactivity of Novel 2‐Substituted Methlthio‐5‐(4‐Amino‐2‐Methylpyrimidin‐5‐yl)‐1,3,4‐Thiadiazole Derivatives

“…In its mass spectrum, the molecular ion peak was noticed m/z at 254. To make an evaluation of the antiviral properties of 2-substituted methlthio-5-(4-amino-2-methylpyrimidin-5-yl)-1,3,4-thiadiazole (9a-9v), the bioassays against TMV have been carried out according to the halfleaf juice-robbing method, with the commercial plat virucide Ningnanmycin used as the control [29]. The antiviral assay (curative, protection, and inactivation) results of all compounds were listed in Table 1.…”

“…To make an evaluation of the antiviral properties of 2‐substituted methlthio‐5‐(4‐amino‐2‐methylpyrimidin‐5‐yl)‐1,3,4‐thiadiazole ( 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i , 9j , 9k , 9l , 9m , 9n , 9o , 9p , 9q , 9r , 9s , 9t , 9u , 9v ), the bioassays against TMV have been carried out according to the half‐leaf juice‐robbing method, with the commercial plat virucide Ningnanmycin used as the control . The antiviral assay (curative, protection, and inactivation) results of all compounds were listed in Table .…”

Towards Small Molecules as Therapies for Alzheimer’s Disease and Other Neurodegenerative Disorders

“…Cognitive improvements were reported for two executive functions [193] while Phase II trials are underway for HD [194]. Investigators have demonstrated that though Deferiprone (61) can enter the brain at low concentration [196] and reduce iron content [197], it is prone to rapid metabolism in the liver [198]. 24, 61) has been clinically approved as a therapy for iron overload and close analogs, designed to overcome its intrinsic metabolically liability, have been reported.…”

Iron Chelation and Multiple Sclerosis

“…And it could redistribute iron within cells, e.g., remove labile iron in mitochondria (Sohn et al, 2008), which could facilitate the management of iron within cells such as those in deep gray matter in MS. In the future, access of chelators to the brain will likely improve as recent studies have investigated ways to increase their permeability into the brain (Roy et al, 2010; Ma et al, 2012; Liddell et al, 2013). …”