Premium
Scoping Studies into the Structure‐Activity Relationship (SAR) of Phenylephrine‐Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
Author(s) -
Cullen Danica R.,
Pengon Jutharat,
Rattanajak Roonglawan,
Chaplin Jason,
Kamchonwongpaisan Sumalee,
Mocerino Mauro
Publication year - 2016
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201601059
Subject(s) - trypanosoma brucei rhodesiense , trypanosoma brucei , african trypanosomiasis , trypanosoma evansi , cytotoxicity , in vitro , antiparasitic , structure–activity relationship , chemistry , biochemistry , trypanosomiasis , biology , pharmacology , virology , medicine , gene , pathology
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 IC 50 value of 0.25 ± 0.02 μM, while also showing low cytotoxicity to mammalian cells.