Inhibition of PDE5A1 guanosine cyclic monophosphate (cGMP) hydrolysing activity by sildenafil analogues that inhibit cellular cGMP efflux.

ABSTRACT:

Objectives

To determine the ability of 11 sildenafil analogues to discriminate between cyclic nucleotide phosphodiesterases (cnPDEs) and to characterise their inhibitory potencies (K_i values) of PDE5A1-dependent guanosine cyclic monophosphate (cGMP) hydrolysis.

Methods

Sildenafil analogues were identified by virtual ligand screening (VLS) and screened for their ability to inhibit adenosine cyclic monophosphate (cAMP) hydrolysis by PDE1A1, PDE1B1, PDE2A1, PDE3A, PDE10A1 and PDE10A2, and cGMP hydrolysis by PDE5A, PDE6C, PDE9A2 for a low (1 nm) and high concentration (10 μm). Complete IC₅₀ plots for all analogues were performed for PDE5A-dependent cGMP hydrolysis. Docking studies and scoring were made using the ICM molecular modelling software.

Key find

SUBMITTER: Subbotina A 

PROVIDER: S-EPMC5434896 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature