ArticleAntimicrobial agents and chemotherapy2007
2,N6-disubstituted adenosine analogs with antitrypanosomal and antimalarial activities.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 46 citations in OpenAlex.
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- Imidazoline- and Benzamidine-Based Trypanosome Alternative Oxidase Inhibitors: Synthesis and Structure-Activity Relationship Studies.ACS medicinal chemistry letters · 2022Article
- The individual components of commercial isometamidium do not possess stronger trypanocidal activity than the mixture, nor bypass isometamidium resistance.International journal for parasitology. Drugs and drug resistance · 2019Article
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- Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds.Drug design, development and therapy · 2019Article
- Drug resistance in protozoan parasites.Emerging topics in life sciences · 2017Article
- The Chemical Characterization of Nigerian Propolis samples and Their Activity Against Trypanosoma brucei.Scientific reports · 2017Article
- Targeting the parasite's DNA with methyltriazenyl purine analogs is a safe, selective, and efficacious antitrypanosomal strategy.Antimicrobial agents and chemotherapy · 2015Article
- SAR Studies of Diphenyl Cationic Trypanocides: Superior Activity of Phosphonium over Ammonium Salts.ACS medicinal chemistry letters · 2015Article
- A new nonpolar N-hydroxy imidazoline lead compound with improved activity in a murine model of late-stage Trypanosoma brucei brucei infection is not cross-resistant with diamidines.Antimicrobial agents and chemotherapy · 2015Article
- Trypanosoma brucei adenine-phosphoribosyltransferases mediate adenine salvage and aminopurinol susceptibility but not adenine toxicity.International journal for parasitology. Drugs and drug resistance · 2014Article
- Pyrimidine biosynthesis is not an essential function for Trypanosoma brucei bloodstream forms.PloS one · 2013Article
- Untargeted metabolomics reveals a lack of synergy between nifurtimox and eflornithine against Trypanosoma brucei.PLoS neglected tropical diseases · 2012Article
- Symmetrical choline-derived dications display strong anti-kinetoplastid activity.The Journal of antimicrobial chemotherapy · 2011Article
- Evaluation of nucleoside hydrolase inhibitors for treatment of African trypanosomiasis.Antimicrobial agents and chemotherapy · 2010Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A library of 2,N(6)-disubstituted adenosine analogs was synthesized and the analogs were tested for their antiprotozoal activities. It was found that 2-methoxy and 2-histamino and N(6)-m-iodobenzyl substitutions generally produced analogs with low levels of antiprotozoal activity. The best antiplasmodial activity was achieved with large aromatic substitutions, such as N(6)-2,2-diphenylethyl and naphthylmethyl, which could indicate a mechanism of action through aromatic stacking with heme in the digestive vacuole of Plasmodium spp. The activities against Trypanosoma cruzi trypomastigotes and Leishmania donovani amastigotes were generally low; but several analogs, particularly those with cyclopentylamino substitutions, displayed potent activities against Trypanosoma brucei rhodesiense and T. b. brucei bloodstream forms in vitro. The most active were 2-cyclopentylamino-N(6)-cyclopentyladenosine (compound NA42) and 2-cyclopentylamino-N(6)-cyclopentyladenine (compound NA134), with the nucleobase an order of magnitude more potent than the nucleoside, at 26 +/- 4 nM. It was determined that the mode of action of these purines was trypanostatic, with the compounds becoming trypanocidal only at much higher concentrations. Those 2,N(6)-disubstituted purines tested for their effects on purine transport in T. b. brucei displayed at best a moderate affinity for the transporters. It is highly probable that the large hydrophobic substitutions, which bestow high calculated octanol-water coefficient values on the analogs, allow them to diffuse across the membrane. Consistent with this view, the analogs were as effective against a T. b. brucei strain lacking the P2 nucleoside transporter as they were against the parental strain. As the analogs were not toxic to human cell lines, the purine analogs are likely to act on a trypanosome-specific target.
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