Systematic Exploration of Functional Group Relevance for Anti-Leishmanial Activity of Anisomycin

Anh Minh Thao Nguyen; Moran Shalev-Benami; Chloé Rosa-Teijeiro; Ana Victoria Ibarra-Meneses; Ada Yonath; Anat Bashan; Charles L. Jaffe; Martin Olivier; Christopher Fernandez-Prada; William D. Lubell

doi:10.3390/biomedicines11092541

Systematic Exploration of Functional Group Relevance for Anti-Leishmanial Activity of Anisomycin

Anh Minh Thao Nguyen^*, Moran Shalev-Benami, Chloé Rosa-Teijeiro, Ana Victoria Ibarra-Meneses, Ada Yonath, Anat Bashan, Charles L. Jaffe, Martin Olivier, Christopher Fernandez-Prada, William D. Lubell^*

^*Corresponding author for this work

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

2 Scopus citations

Abstract

Assessment of structure–activity relationships for anti-protozoan activity revealed a strategy for preparing potent anisomycin derivatives with reduced host toxicity. Thirteen anisomycin analogs were synthesized by modifying the alcohol, amine, and aromatic functional groups. Examination of anti-protozoal activity against various strains of Leishmania and cytotoxicity against leucocytes with comparison against the parent natural product demonstrated typical losses of activity with modifications of the alcohol, amine, and aromatic meta-positions. On the other hand, the para-phenol moiety of anisomycin proved an effective location for introducing substituents without significant loss of anti-protozoan potency. An entry point for differentiating activity against Leishmania versus host has been uncovered by this systematic study.

Original language	English
Article number	2541
Journal	Biomedicines
Volume	11
Issue number	9
DOIs	https://doi.org/10.3390/biomedicines11092541
State	Published - Sep 2023
Externally published	Yes

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Publisher Copyright:
© 2023 by the authors.

Keywords

anisomycin
Leishmania
ribosome

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10.3390/biomedicines11092541

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title = "Systematic Exploration of Functional Group Relevance for Anti-Leishmanial Activity of Anisomycin",

abstract = "Assessment of structure–activity relationships for anti-protozoan activity revealed a strategy for preparing potent anisomycin derivatives with reduced host toxicity. Thirteen anisomycin analogs were synthesized by modifying the alcohol, amine, and aromatic functional groups. Examination of anti-protozoal activity against various strains of Leishmania and cytotoxicity against leucocytes with comparison against the parent natural product demonstrated typical losses of activity with modifications of the alcohol, amine, and aromatic meta-positions. On the other hand, the para-phenol moiety of anisomycin proved an effective location for introducing substituents without significant loss of anti-protozoan potency. An entry point for differentiating activity against Leishmania versus host has been uncovered by this systematic study.",

keywords = "anisomycin, Leishmania, ribosome",

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doi = "10.3390/biomedicines11092541",

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AU - Nguyen, Anh Minh Thao

AU - Shalev-Benami, Moran

AU - Rosa-Teijeiro, Chloé

AU - Ibarra-Meneses, Ana Victoria

AU - Yonath, Ada

AU - Bashan, Anat

AU - Jaffe, Charles L.

AU - Olivier, Martin

AU - Fernandez-Prada, Christopher

AU - Lubell, William D.

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N2 - Assessment of structure–activity relationships for anti-protozoan activity revealed a strategy for preparing potent anisomycin derivatives with reduced host toxicity. Thirteen anisomycin analogs were synthesized by modifying the alcohol, amine, and aromatic functional groups. Examination of anti-protozoal activity against various strains of Leishmania and cytotoxicity against leucocytes with comparison against the parent natural product demonstrated typical losses of activity with modifications of the alcohol, amine, and aromatic meta-positions. On the other hand, the para-phenol moiety of anisomycin proved an effective location for introducing substituents without significant loss of anti-protozoan potency. An entry point for differentiating activity against Leishmania versus host has been uncovered by this systematic study.

AB - Assessment of structure–activity relationships for anti-protozoan activity revealed a strategy for preparing potent anisomycin derivatives with reduced host toxicity. Thirteen anisomycin analogs were synthesized by modifying the alcohol, amine, and aromatic functional groups. Examination of anti-protozoal activity against various strains of Leishmania and cytotoxicity against leucocytes with comparison against the parent natural product demonstrated typical losses of activity with modifications of the alcohol, amine, and aromatic meta-positions. On the other hand, the para-phenol moiety of anisomycin proved an effective location for introducing substituents without significant loss of anti-protozoan potency. An entry point for differentiating activity against Leishmania versus host has been uncovered by this systematic study.

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KW - Leishmania

KW - ribosome

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Systematic Exploration of Functional Group Relevance for Anti-Leishmanial Activity of Anisomycin

Abstract

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Keywords

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