Triazoxins: Novel nucleosides with anti-Giardia activity

Praveen K. Pogula; Atasi De Chatterjee; Miguel Chi; Harrison W. VanKoten; Siddhartha Das; Steven E. Patterson

doi:10.1016/j.bmcl.2020.127175

Triazoxins: Novel nucleosides with anti-Giardia activity

Praveen K. Pogula, Atasi De Chatterjee, Miguel Chi, Harrison W. VanKoten, Siddhartha Das, Steven E. Patterson

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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	https://doi.org/10.1016/j.bmcl.2020.127175
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.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

Anti-giardiasis
Cyst
Giardia
Phosphonoxin
Triazoxin
Trophozoite

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural

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10.1016/j.bmcl.2020.127175

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title = "Triazoxins: Novel nucleosides with anti-Giardia activity",

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.",

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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. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

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AU - Das, Siddhartha

AU - Patterson, Steven E.

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Triazoxins: Novel nucleosides with anti-Giardia activity

Abstract

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Keywords

PubMed: MeSH publication types

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