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Antimicrob Agents Chemother. 2018 Oct 24;62(11). pii: e00786-18. doi: 10.1128/AAC.00786-18. Print 2018 Nov.

Activity of Aromathecins against African Trypanosomes.

Author information

1
Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2
Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA.
3
Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA tshapiro@jhmi.edu.

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:

Trypanosoma brucei; aromathecin; sleeping sickness; structure-activity; topoisomerase

PMID:
30104277
PMCID:
PMC6201061
[Available on 2019-04-24]
DOI:
10.1128/AAC.00786-18

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