Abstract
Novel nucleoside analogues named “triazoxins” were synthesized. Of these, two analogues were found to be highly effective against Giardia lamblia, an intestinal parasite and a major cause of waterborne infection, worldwide. While compound 7 reduced the growth of trophozoites in culture (IC50, ~5 μM), compound 21 blocked the in vitro cyst production (IC50 ~5 μM). Compound 21 was also effective against trophozoites (IC50, ~36 μM). A third analogue (compound 8) was effective against both trophozoites (IC50, ~36 μM) and cysts (IC50, ~20 μM) although at higher concentration. Thus triazoxin analogues are unique and exhibit morphology (i.e., trohozoites or cysts) -specific effects against Giardia.
Original language | English (US) |
---|---|
Article number | 127175 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 30 |
Issue number | 12 |
DOIs | |
State | Published - Jun 15 2020 |
Bibliographical note
Funding Information:We thank the Center for Drug Design, and NIH- NIAID grant 1R21AI138061 for funding this project. Cellular experiments were carried out in the Border Biomedical Research Center (BBRC) core Facility at the University of Texas at El Paso supported by a grant ( G12MD0075592 ) from the NIMHD (NIH). ADC and SD were supported partly by a grant ( R01AI095667 ) from the NIH ( NIAID ). MC was supported by NIH-RISE Grant 5R25GM069621 .
Funding Information:
We thank the Center for Drug Design, and NIH-NIAID grant 1R21AI138061 for funding this project. Cellular experiments were carried out in the Border Biomedical Research Center (BBRC) core Facility at the University of Texas at El Paso supported by a grant (G12MD0075592) from the NIMHD (NIH). ADC and SD were supported partly by a grant (R01AI095667) from the NIH (NIAID). MC was supported by NIH-RISE Grant 5R25GM069621.
Keywords
- Anti-giardiasis
- Cyst
- Giardia
- Phosphonoxin
- Triazoxin
- Trophozoite