Assessment of PDE5 Inhibitory Activity of Novel Compounds for Potential Therapeutic Applications in Alzheimer’s Disease

Student Presenter(s): Ahnaf Zaman and Justin Edward
Faculty Mentor: Jole Fiorito
School/College: Arts and Sciences, Old Westbury

This research study aims to determine the IC-50 values of four phosphodiesterase 5 (PDE5) inhibitors, namely II-47, II-58, II-51, and II-53. PDE5 is an isoform of the phosphodiesterase enzyme family that selectively cleaves cGMP to GMP. It has been shown that PDE5 has a role in the transcriptional regulation of proteins that affect neurogenesis and synaptic plasticity. The inhibitors were tested against PDE5 enzyme activity using a high-performance liquid chromatography-mass spectrometry, and the concentration required to inhibit 50% of enzyme activity was determined. The results showed that all four compounds exhibited inhibitory activity against PDE5, with IC50 values ranging from 1.37 to 15.46 uM. In particular, II-51 exhibited the highest potency among the inhibitors tested, with an IC50 value of 1.37 uM. This advances research for potential applications of PDE5 inhibitors such as Alzheimer’s Disease and other related disorders.