Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense

摘要

abstract_textpHuman 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 mu M, while also showing low cytotoxicity to mammalian cells./p/abstract_text