Picture of a black hole

Strathclyde Open Access research that creates ripples...

The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of research papers by University of Strathclyde researchers, including by Strathclyde physicists involved in observing gravitational waves and black hole mergers as part of the Laser Interferometer Gravitational-Wave Observatory (LIGO) - but also other internationally significant research from the Department of Physics. Discover why Strathclyde's physics research is making ripples...

Strathprints also exposes world leading research from the Faculties of Science, Engineering, Humanities & Social Sciences, and from the Strathclyde Business School.

Discover more...

Efficacy of anti-neoplastic drugs against acanthamoeba

Beattie, T.K. and Tomlinson, A. and Seal, D. (2003) Efficacy of anti-neoplastic drugs against acanthamoeba. Investigative Ophthalmology and Visual Science. ISSN 0146-0404

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

Purpose:Late presenting cases of Acanthamoeba keratitis are particularly difficult to treat. The organism can persist, despite treatment with chlorhexidine or PHMB, maintaining an active infection. New drug therapies with enhanced activity are therefore needed to treat this painful, potentially blinding infection. This study was undertaken to determine the efficacy of three anti–cancer drugs against Acanthamoeba. Methods:Doubling dilutions of MGBG [10–0.15mg/ml (38.5–0.6mM)], CHS 828 [660–10µg/ml (1782–27µM)] and hexadecyl–phosphocholine [HePC, Miltefosine; 660–10µg/ml (1782–27µM)] were tested alone or in combination with chlorhexidine, PHMB and propamidine, for efficacy against Acanthamoeba castellanii trophozoites or cysts. Sensitivity assays were performed over 48h in 96–well microtitre plates. Results: MGBG killed trophozoites at 300µg/ml (1.2mM) and cysts at 1250µg/ml (4.6mM). The combination drugs had no effect on the cysticidal concentration of MGBG, but PHMB and propamidine may have an additive effect against trophozoites. CHS 828 caused rounding up of trophozoites, but had no effect on amoebal viability. HePC killed both trophozoites and cysts at 330µg/ml (0.8µM). Against trophozoites, propamidine had an additive effect on HePC reducing the inhibitory concentration to 82µg/ml (0.2mM) and 165µg/ml (0.4mM) when added at high (4µg/ml) and low (1µg/ml) concentrations, respectively. Synergy between HePC and the combination drugs was found against cysts, being most active for chlorhexidine when added at a concentration of 2µg/ml, reducing the minimum cysticidal concentration of HePC to <10µg/ml. Conclusions:At the concentrations tested CHS 828 did not demonstrate any amoebicidal activity and as such is unlikely to be a potential therapeutic agent. The concentration of MGBG required to eradicate cysts may prevent its use in therapy. HePC shows potential as a therapeutic agent as synergy was demonstrated between HePC and the biguanides against cysts, but there may be some antagonism against trophozoites. Further work is necessary to determine the full potential of HePC as a therapeutic agent in the treatment of Acanthamoeba infection, in particular keratitis.