The novel cyclophilin inhibitor C105SR reduces hepatic ischaemia-reperfusion injury via mitoprotection.

ABSTRACT:

Background & aims

Mitochondrial permeability transition pore (mPTP) opening is critical for mediating cell death during hepatic ischaemia-reperfusion injury (IRI). Blocking mPTP opening by inhibiting cyclophilin D (CypD) is a promising pharmacological approach for the treatment of IRI. Here, we show that diastereoisomers of a new class of small-molecule cyclophilin inhibitors (SMCypIs) have properties that make them attractive candidates for the development of therapeutic agents against liver IRI.

Methods

Derivatives of the parent SMCypI were synthesised and evaluated for their ability to inhibit CypD peptidyl-prolyl cis-trans isomerase (PPIase) activity and for their mitoprotective properties, evaluated by measuring mitochondrial swelling and calcium retention

SUBMITTER: Kheyar A 

PROVIDER: S-EPMC10582583 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature