4-Chloroisocoumarins as Chlamydial Protease Inhibitors and Anti-Chlamydial Agents

Matthew J A Phillips; Wilhelmina M Huston; Andrew M McDonagh; Tristan Rawling

doi:10.3390/molecules29071519

4-Chloroisocoumarins as Chlamydial Protease Inhibitors and Anti-Chlamydial Agents

Molecules. 2024 Mar 28;29(7):1519. doi: 10.3390/molecules29071519.

Authors

Matthew J A Phillips¹, Wilhelmina M Huston², Andrew M McDonagh¹, Tristan Rawling¹

Affiliations

¹ School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, Australia.
² School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW 2007, Australia.

Abstract

4-Chloroisocoumarin compounds have broad inhibitory properties against serine proteases. Here, we show that selected 3-alkoxy-4-chloroisocoumarins preferentially inhibit the activity of the conserved serine protease High-temperature requirement A of Chlamydia trachomatis. The synthesis of a new series of isocoumarin-based scaffolds has been developed, and their anti-chlamydial properties were investigated. The structure of the alkoxy substituent was found to influence the potency of the compounds against High-temperature requirement A, and modifications to the C-7 position of the 3-alkoxy-4-chloroisocoumarin structure attenuate anti-chlamydial properties.

Keywords: anti-chlamydial; isocoumarin; protease inhibitor.

MeSH terms

Alcohols*
Chlamydia trachomatis*
Enzyme Therapy
Isocoumarins
Protease Inhibitors* / pharmacology
Serine Endopeptidases
Serine Proteases

Substances

alkoxyl radical
Protease Inhibitors
Isocoumarins
Serine Endopeptidases
Serine Proteases
Alcohols

Grants and funding

This research received no external funding.