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

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 scaf...

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Main Authors: Cullen, Danica, Pengon, J., Rattanajak, R., Chaplin, J., Kamchonwongpaisan, S., Mocerino, Mauro
Format: Journal Article
Published: Wiley - V C H Verlag GmbH & Co. KGaA 2016
Online Access:http://hdl.handle.net/20.500.11937/51609
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author Cullen, Danica
Pengon, J.
Rattanajak, R.
Chaplin, J.
Kamchonwongpaisan, S.
Mocerino, Mauro
author_facet Cullen, Danica
Pengon, J.
Rattanajak, R.
Chaplin, J.
Kamchonwongpaisan, S.
Mocerino, Mauro
author_sort Cullen, Danica
building Curtin Institutional Repository
collection Online Access
description 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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publishDate 2016
publisher Wiley - V C H Verlag GmbH & Co. KGaA
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spelling curtin-20.500.11937-516092017-06-20T05:49:43Z Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense Cullen, Danica Pengon, J. Rattanajak, R. Chaplin, J. Kamchonwongpaisan, S. Mocerino, Mauro 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. 2016 Journal Article http://hdl.handle.net/20.500.11937/51609 Wiley - V C H Verlag GmbH & Co. KGaA restricted
spellingShingle Cullen, Danica
Pengon, J.
Rattanajak, R.
Chaplin, J.
Kamchonwongpaisan, S.
Mocerino, Mauro
Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
title Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
title_full Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
title_fullStr Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
title_full_unstemmed Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
title_short Scoping Studies into the Structure-Activity Relationship (SAR) of Phenylephrine-Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense
title_sort scoping studies into the structure-activity relationship (sar) of phenylephrine-derived analogues as inhibitors of trypanosoma brucei rhodesiense
url http://hdl.handle.net/20.500.11937/51609