Activity of aromathecins against African trypanosomes

Nathaniel P. Nenortas; Maris A. Cinelli; Andrew E. Morrell; Mark Cushman; Theresa A. Shapiro

doi:10.1128/AAC.00786-18

Activity of aromathecins against African trypanosomes

Nathaniel P. Nenortas, Maris A. Cinelli, Andrew E. Morrell, Mark Cushman, Theresa A. Shapiro

School of Medicine

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

3 Scopus citations

Abstract

African sleeping sickness is responsible for thousands of deaths annually, and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African trypanosomes. The compounds had selectively toxic antiparasitic potency, in situ poisoning activity against the phylogenetically unique topoisomerase in these parasites, and a representative compound intercalated into DNA with micromolar affinity. DNA intercalation and topoisomerase poisoning may contribute to the antitrypanosomal activity of aromathecins.

Original language	English (US)
Article number	e00786-18
Journal	Antimicrobial agents and chemotherapy
Volume	62
Issue number	11
DOIs	https://doi.org/10.1128/AAC.00786-18
State	Published - Nov 2018

Keywords

Aromathecin
Sleeping sickness
Structure-activity
Topoisomerase
Trypanosoma brucei

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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10.1128/AAC.00786-18

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title = "Activity of aromathecins against African trypanosomes",

abstract = "African sleeping sickness is responsible for thousands of deaths annually, and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African trypanosomes. The compounds had selectively toxic antiparasitic potency, in situ poisoning activity against the phylogenetically unique topoisomerase in these parasites, and a representative compound intercalated into DNA with micromolar affinity. DNA intercalation and topoisomerase poisoning may contribute to the antitrypanosomal activity of aromathecins.",

keywords = "Aromathecin, Sleeping sickness, Structure-activity, Topoisomerase, Trypanosoma brucei",

author = "Nenortas, {Nathaniel P.} and Cinelli, {Maris A.} and Morrell, {Andrew E.} and Mark Cushman and Shapiro, {Theresa A.}",

note = "Funding Information: We thank Beth Nenortas and Rahul Bakshi for their assistance with this work and for reading the manuscript, as well as Emily Caton for technical assistance. This work was supported by NIH/NIAID grants AI028855 and AI095453 (both to T.A.S.) and by NIH/NCI grants U01CA089566 and P30CA023168 (both to M.C.). Publisher Copyright: {\textcopyright} 2018 American Society for Microbiology. All Rights Reserved.",

year = "2018",

month = nov,

doi = "10.1128/AAC.00786-18",

language = "English (US)",

volume = "62",

journal = "Antimicrobial Agents and Chemotherapy",

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AU - Cinelli, Maris A.

AU - Morrell, Andrew E.

AU - Cushman, Mark

AU - Shapiro, Theresa A.

N1 - Funding Information: We thank Beth Nenortas and Rahul Bakshi for their assistance with this work and for reading the manuscript, as well as Emily Caton for technical assistance. This work was supported by NIH/NIAID grants AI028855 and AI095453 (both to T.A.S.) and by NIH/NCI grants U01CA089566 and P30CA023168 (both to M.C.). Publisher Copyright: © 2018 American Society for Microbiology. All Rights Reserved.

PY - 2018/11

Y1 - 2018/11

N2 - African sleeping sickness is responsible for thousands of deaths annually, and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African trypanosomes. The compounds had selectively toxic antiparasitic potency, in situ poisoning activity against the phylogenetically unique topoisomerase in these parasites, and a representative compound intercalated into DNA with micromolar affinity. DNA intercalation and topoisomerase poisoning may contribute to the antitrypanosomal activity of aromathecins.

AB - African sleeping sickness is responsible for thousands of deaths annually, and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African trypanosomes. The compounds had selectively toxic antiparasitic potency, in situ poisoning activity against the phylogenetically unique topoisomerase in these parasites, and a representative compound intercalated into DNA with micromolar affinity. DNA intercalation and topoisomerase poisoning may contribute to the antitrypanosomal activity of aromathecins.

KW - Aromathecin

KW - Sleeping sickness

KW - Structure-activity

KW - Topoisomerase

KW - Trypanosoma brucei

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Activity of aromathecins against African trypanosomes

Abstract

Keywords

ASJC Scopus subject areas

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