Screening For Inhibitors Of Essential Leishmania Glucose Transporters

Abstract

The major objective of this project is to identify compounds that function as selective inhibitors of the essential glucose transporters of the parasite Leishmania mexicana. Toward this end, a cell growth assay has been developed that can be employed in a high throughput screen (HTS) for such inhibitors. The dye SYBR green has been identified as the optimal reagent for following cell growth by fluorescence. The assay has been optimized initially for a 96-well plate assay and subsequently for a higher density 384-well plate assay. Statistical criteria have been employed to demonstrate that the assay functions with high accuracy and reproducibility under control conditions, with a Z -factor of approximately 0.9. This assay was subsequently employed in a scaling screen of the 2000 compound MicroSource Discovery Spectrum Collection to yield a Z-factor of 0.84 in the screen of a real library. The high quality of the assay indicates that it is ready to proceed to an HTS of a much larger library. The assay has been transferred to the HTS facility at St. Jude Children s Research Hospital in Memphis, TN to initiate full high throughput screens.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2011
Accession Number
ADA551900

Entities

People

  • Scott M. Landfear

Organizations

  • Oregon Health & Science University

Tags

DTIC Thesaurus Topics

  • Blood
  • Cell Line
  • Cells
  • Chemistry
  • Department Of Defense
  • Drug Therapy
  • Dynamic Range
  • Health Services
  • Leishmania
  • Leishmaniasis
  • Malaria
  • Measurement
  • Medical Personnel
  • Parasites
  • Parasitology
  • Spreadsheet Software
  • Therapy

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Molecular and Cellular Biochemistry
  • Oncology and Biomarker-Based Cancer Detection.