A new chemotype with promise against Trypanosoma cruzi

Xiaofang Wang; Monica Cal; Marcel Kaiser; Frederick S. Buckner; Galina I. Lepesheva; Austin G. Sanford; Alexander I. Wallick; Paul H. Davis; Jonathan L. Vennerstrom

doi:10.1016/j.bmcl.2019.126778

A new chemotype with promise against Trypanosoma cruzi

Xiaofang Wang, Monica Cal, Marcel Kaiser, Frederick S. Buckner, Galina I. Lepesheva, Austin G. Sanford, Alexander I. Wallick, Paul H. Davis, Jonathan L. Vennerstrom

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

2 Scopus citations

Abstract

Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure–activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.

Original language	English (US)
Article number	126778
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2019.126778
State	Published - Jan 1 2020

Keywords

Chagas disease
SAR
Trypanosoma cruzi

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2019.126778

Cite this

@article{096bbbfa49ca41a0b62e66feb87d7e42,

title = "A new chemotype with promise against Trypanosoma cruzi",

abstract = "Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure–activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.",

keywords = "Chagas disease, SAR, Trypanosoma cruzi",

author = "Xiaofang Wang and Monica Cal and Marcel Kaiser and Buckner, {Frederick S.} and Lepesheva, {Galina I.} and Sanford, {Austin G.} and Wallick, {Alexander I.} and Davis, {Paul H.} and Vennerstrom, {Jonathan L.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2020",

month = jan,

day = "1",

doi = "10.1016/j.bmcl.2019.126778",

language = "English (US)",

volume = "30",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "1",

}

TY - JOUR

T1 - A new chemotype with promise against Trypanosoma cruzi

AU - Wang, Xiaofang

AU - Cal, Monica

AU - Kaiser, Marcel

AU - Buckner, Frederick S.

AU - Lepesheva, Galina I.

AU - Sanford, Austin G.

AU - Wallick, Alexander I.

AU - Davis, Paul H.

AU - Vennerstrom, Jonathan L.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure–activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.

AB - Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of ≥10. The initial structure–activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.

KW - Chagas disease

KW - SAR

KW - Trypanosoma cruzi

UR - http://www.scopus.com/inward/record.url?scp=85075461372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075461372&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2019.126778

DO - 10.1016/j.bmcl.2019.126778

M3 - Article

C2 - 31706668

AN - SCOPUS:85075461372

SN - 0960-894X

VL - 30

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 1

M1 - 126778

ER -

A new chemotype with promise against Trypanosoma cruzi

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this