Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
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Human African Trypanosomiasis (HAT) is a disease caused by the parasite Trypanosoma brucei and is classified as a neglected tropical disease of concern in sub-Saharan Africa. A scoping study has been undertaken to develop a preliminary structure activity relationship of a tetrahydroisoquinoline scaffold. Fourteen compounds based around this core scaffold were synthesised and evaluated for their activity against Trypanosoma brucei rhodesiense in vitro. Initial results are promising with a number of analogues showing low micromolar inhibition of T.b.rhodesiense with acceptable selectivity over mammalian cells. The most promising is a secondary amine analogue showing the most potent inhibition of T.b.rhodesiense, with an IC50 value of 0.25 ± 0.02 µM, while also showing low cytotoxicity to mammalian cells.
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Development of tetrahydroisoquinoline analogues: Towards a treatment for Human African TrypanosomiasisCullen, Danica Renae (2016)This research describes the exploration of a new scaffold with the potential to be developed in to a new drug for the treatment of Human African Trypanosomiasis (HAT), a neglected disease endemic in sub-Saharan Africa. ...
Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinolineCullen, Danica; Pengon, J.; Rattanajak, R.; Chaplin, J.; Kamchonwongpaisan, S.; Massera, C.; Mocerino, Mauro; Rohl, Andrew (2017)Condensation of phenylephrine with different aldehydes, under Pictet-Spengler cyclisation conditions, afforded a series of tetrahydroisoquinoline derivatives as mixtures of cis/trans isomers. Single crystal X-ray analysis ...