Lipophilic mediated assays for beta-hematin inhibitors

Comb Chem High Throughput Screen. 2010 Mar;13(3):285-92. doi: 10.2174/138620710790980496.

Abstract

The growing drug resistance of Plasmodia spp. to current antimalarial agents in the quinine and artemisinin families further asserts the need for novel drug classes to combat malaria infection. One approach to the discovery of new antimalarials is the screening of natural product extracts for activity against the formation of hemozoin, a biomineral essential to parasite survival. By mimicking the in vivo lipid-water interface at which native hemozoin is found, hemozoin can be synthesized outside the parasite. In this work, a variety of lipophilic mediators was used to determine the optimal platform for in vitro hemozoin formation and then tested for efficacy in preliminary screens containing crude natural product extracts. The complete optimization and validation of a NP-40 detergent-mediated assay provide a screening template with an expedited 4-hour incubation time and identical IC50 values to those measured from the parasite's native lipid component.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Validation Study

MeSH terms

  • Actinobacteria / metabolism
  • Antimalarials / isolation & purification
  • Antimalarials / pharmacology*
  • Biological Products / isolation & purification
  • Biological Products / pharmacology*
  • Hemeproteins / antagonists & inhibitors*
  • Hemeproteins / metabolism*
  • High-Throughput Screening Assays / methods*
  • Humans
  • Malaria / drug therapy*
  • Plasmodium / metabolism*
  • Surface-Active Agents / metabolism

Substances

  • Antimalarials
  • Biological Products
  • Hemeproteins
  • Surface-Active Agents
  • hemozoin