Molecular study of mechanisms of action of cilostazol on certain families of phosphodiesterases
K. A. Koreyba, Victor Stupin, Ekaterina Silina, K.N. Syuzev, O. A. Serebryakova
Abstract
OBJECTIVE: The purpose of the study was to examine the effect of cilostazol on isoforms of targets of phosphodiesterase 3 and phosphodiesterase 5 by means of molecular modeling. MATERIAL AND METHODS: kcal · mol 1 · K 1) and T is the temperature (298.15 К). RESULTS: Cilostazol possesses higher affinity to isoform of PDE3A (Ki=54 nM) as compared with PDE3B (Ki=1.13 μM) based on the findings of the performed molecular docking. Also, cilostazol can inhibit PDE5 in therapeutic doses (Ki=10 μM). CONCLUSION: Cilostazol-mediated inhibition of the isoform PDE3A to a greater degree than PDE3B explains a low incidence of side effects from the side of PDE3B inhibition in clinical practice. Cilostazol may also inhibit PDE5 at therapeutic doses (Ki=10 μM), in which connection it may have an additional therapeutic effect in treatment of intermittent claudication, diabetes mellitus and its complications, especially neuropathy.