Thiazolino 2-Pyridone Amide Isosteres As Inhibitors of Chlamydia trachomatis Infectivity

James A D Good; Martina Kulén; Jim Silver; K Syam Krishnan; Wael Bahnan; Carlos Núñez-Otero; Ingela Nilsson; Emma Wede; Esmee de Groot; Åsa Gylfe; Sven Bergström; Fredrik Almqvist

doi:10.1021/acs.jmedchem.7b00716

Thiazolino 2-Pyridone Amide Isosteres As Inhibitors of Chlamydia trachomatis Infectivity

J Med Chem. 2017 Nov 22;60(22):9393-9399. doi: 10.1021/acs.jmedchem.7b00716. Epub 2017 Nov 3.

Authors

James A D Good^{1

2}, Martina Kulén^{1

2}, Jim Silver^{2

3

4}, K Syam Krishnan^{1

2}, Wael Bahnan^{2

3

4}, Carlos Núñez-Otero^{2

4

5}, Ingela Nilsson^{2

3

4}, Emma Wede^{2

3

4}, Esmee de Groot^{2

3

4}, Åsa Gylfe^{2

4

5}, Sven Bergström^{2

3

4}, Fredrik Almqvist^{1

2}

Affiliations

¹ Department of Chemistry, Umeå University , 901 87 Umeå, Sweden.
² Umeå Centre for Microbial Research, Umeå University , 901 87 Umeå, Sweden.
³ Department of Molecular Biology, Umeå University , 901 87 Umeå, Sweden.
⁴ Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University , 901 87 Umeå, Sweden.
⁵ Clinical microbiology, Umeå University , 901 85 Umeå, Sweden.

PMID: 29053275
DOI: 10.1021/acs.jmedchem.7b00716

Abstract

Chlamydia trachomatis is a global health burden due to its prevalence as a sexually transmitted disease and as the causative agent of the eye infection trachoma. We recently discovered 3-amido thiazolino 2-pyridones which attenuated C. trachomatis infectivity without affecting host cell or commensal bacteria viability. We present here the synthesis and evaluation of nonhydrolyzable amide isosteres based on this class, leading to highly potent 1,2,3-triazole based infectivity inhibitors (EC₅₀ ≤ 20 nM).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemical synthesis
Amides / pharmacology*
Amides / toxicity
Antifungal Agents / chemical synthesis
Antifungal Agents / pharmacology*
Antifungal Agents / toxicity
Chlamydia trachomatis / drug effects*
Chlamydia trachomatis / pathogenicity
HeLa Cells
Humans
Mutagenicity Tests
Pyridones / chemical synthesis
Pyridones / pharmacology*
Pyridones / toxicity
Thiazoles / chemical synthesis
Thiazoles / pharmacology*
Thiazoles / toxicity

Substances

Amides
Antifungal Agents
Pyridones
Thiazoles