Purine Transporters as Efficient Carriers for Anti-kinetoplastid Molecules: 3′-Deoxytubercidin versus Trypanosomes

Abstract

After a growing interest in the function of purine transporters in protozoa during the 1990s and early 2000s, the area experienced a lull phase. Recently, however, the potential of tubercidin derivatives, particularly 3′-deoxytubercidin, to cure Trypanosoma brucei infection seems to have started a new wave of interest in the subject, with a large number of newly designed compounds and extensive in vitro testing against T. brucei, Trypanosoma cruzi, and Leishmania spp. Understanding the biochemical properties of purine transporters and using them as drug carriers seem to be emerging once again as a valuable tactic in the fight against neglected diseases.

Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies

“…T. brucei and other trypanosomatid organisms are incapable of de novo purine biosynthesis and need to salvage them from the host [268,269]. An understanding of the purine salvage machinery enables the development of drug targets [270].…”

“…However, tubercidin is toxic to mammalian cells [276,277]. A hybrid molecule between cordycepin and tubercidin has brought about the 3 -deoxy-7-deazaadenosine analogues, which are effective against trypanosomes in mouse models, with 3-deoxytubercidin being identified as the most promising of the 3 -deoxy-7deazaadenosine analogue derivatives [269,277]. Derivatives of 3 -deoxy-7-deazaadenosine, referred to as C6-0-alkylated 7-deazainosine analogues, have been identified as trypanocides, with potential to be developed further along the pipeline of trypanosomiasis drugs [278].…”

Exploring Different Drug Targets Responsible for the Inhibitory Activity of N, N′-Substituted Diamine Derivatives in Leishmania

“…The sequencing, availability and accessibility of the complete Leishmania genome have provided voluminous data necessary for anti-leishmanicidal drug development [4]. The reliance on the differences in the biochemistry and physiology of the host and pathogen in target identification has now been completely replaced by several computational approaches.…”