Screening for Inhibitors of Essential Leishmania Glucose Transporters.

摘要

The objective of this project was to identify compounds that selectively inhibit the essential Leishmania glucose transporters and could hence serve as starting points for development of novel anti-leishmanial drugs. A primary high throughput assay and several secondary assays were developed and optimized for this purpose. From the primary assay, 2804 compounds were identified as hits, compounds that strongly inhibited growth of Leishmania mexicana promastigotes (insect form parasites grown in culture) at approximately 10 M concentration. From the secondary assay that monitored uptake of radiolabeled glucose through the L. mexicana glucose transporter LmxGT2, 162 secondary hits were identified among the 2804 primary hits that strongly inhibited uptake. From a further use of the secondary assay in a dose-response mode, 34 tertiary hits were identified among the 162 secondary hits that inhibited uptake of radiolabeled glucose through LmxGT2 with IC50 values.