Preparation, anti-trypanosomal activity and localisation of a series of dipeptide-based vinyl sulfones

Author(s): William Doherty ¹ ^, ² ^, ³ ^, ⁴ , Jinju James ¹ ^, ² ^, ³ ^, ⁴ , Paul Evans ¹ ^, ² ^, ³ ^, ⁴ , Laura Martin ⁵ ^, ⁶ ^, ⁷ ^, ⁸ , Nikoletta Adler ⁵ ^, ⁶ ^, ⁷ ^, ⁸ , Derek Nolan ⁵ ^, ⁶ ^, ⁷ ^, ⁸ , Andrew Knox ⁵ ^, ⁶ ^, ⁷ ^, ⁸

Publication date (Electronic): 2014

Journal: Org. Biomol. Chem.

Publisher: Royal Society of Chemistry (RSC)

Read this article at

ScienceOpenPublisher

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

An improved, Weinreb amide-based, synthesis of anti-trypanosomal lysine-containing vinyl sulfones is described incorporating, as a feature, diversity at the ε-lysine amino group.

Abstract

An improved, Weinreb amide-based, synthesis of anti-trypanosomal lysine-containing vinyl sulfones is described incorporating, as a feature, diversity at the ε-lysine amino group. Members of this family demonstrated moderate to good efficacy as anti-trypanosomal agents and a fluorescent dansyl ( 19) derivative was used to investigate subcellular localisation of the compound class.

Related collections

Most cited references 43

Record: found
Abstract: found
Article: not found

The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro.

B Räz, M Iten, Y Grether-Bühler … (1997)

Alamar Blue, an indicator for metabolic cell function, was evaluated as a fluorescent and as a colorimetric dye in drug sensitivity assays for human pathogenic African trypanosomes, Trypanosoma brucei rhodesiense and T.b. gambiense. The experimental conditions were adjusted to find those where the relationship between trypanosome number and Alamar Blue signal was linear over the widest possible range. Fluorescent signals correlated to trypanosome numbers from 10(4) trypanosomes/ml (T.b. rhodesiense) and 10(5) trypanosomes/ml (T.b. gambiense) up to 2-3 x 10(6) trypanosomes/ml when trypanosomes were incubated for 2 h with 10% Alamar Blue. Trypanocidal activity of common drugs (melarsoprol, DFMO, suramin, pentamidine and diminazene aceturate) was determined employing this assay. The IC50 values obtained were comparable to those obtained with another fluorochrome, BCECF-AM. The Alamar Blue assay can be applied for drug screening, since it is simple, reproducible and economical. The assay can also be used in field sites with less equipped laboratories, because in addition to fluorometric endpoint determination, a colorimetric reading is possible.