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Mechanism of Action of Praziquantel (PZQ)
SRI is elucidating the mechanism of action of the drug of choice for the treatment of all known forms of human schistosomiasis.
SRI’s Webb Laboratory has recently initiated a multisite collaboration to elucidate the mechanism of action of the widely used anthelmintic drug praziquantel (PZQ), which is the drug of choice for the treatment of all known forms of human schistosomiasis (an infectious disease caused by a type of parasitic worm). At least 250 million people globally are infected with this disease, primarily in tropical climates.
Resistance to PZQ is expected to develop into a significant problem, making improved understanding of its precise mode of action an important human health issue. We are developing the synthesis of optically pure modified PZQ analogs—new affinity labels related to PZQ as well as fluorescent PZQ analogs—to use as tools to delineate the molecular target of PZQ with collaborators at the University of New Mexico.
About the Image
A–D: Six-week p.i. male schistosomes at 88x magnification stained with (A) DAPI (B) DAPI and BODIPY, (C) mPZQ-BODIPY and DAPI and (D) mPZQ-BODIPY with DAPI staining optically removed. E–H: Six-week p.i. female schistosomes at 353x magnification stained with (E) DAPI, (F) DAPI and BODIPY, (G) mPZQ-BODIPY and DAPI and (H) mPZQ-BODIPY with DAPI staining optically removed. I–L: Four-week p.i. mixed sex schistosomes at 353x magnification stained with (I) DAPI, (J) DAPI and BODIPY, (K) mPZQ-BODIPY and DAPI and (L) mPZQ-BODIPY with DAPI staining optically removed. DAPI stain is blue; BODIPY and mPZQ-BODIPY are green.
Image credit: Aragon AD, Imani RA, Blackburn VR, Cupit PM, Melman SD, Goronga T, Webb TR, Loker ES, Cunningham C. Towards an understanding of the mechanism of action of praziquantel. Mol. Biochem. Parasitol. 164:57-65, 2009.
The project described is supported by funds provided under a Grant, Award Number R01AI08707, from the NIH and a subaward from the University of New Mexico.