title: Identification of chalcones as potent and selective PDE5A1 inhibitors.
abstract: Chalcones have an affinity for many receptors, enzymes, and transcription factors as flavonoid analogues. Their most studied pharmacological action is that of vasodilatation due to inhibition of phosphodiesterase 5A1 (PDE5A1). To this end, we have established a recursive partitioning model with 3 chemical descriptors for the prediction of compounds that can inhibit PDE5A1. This model was able to predict active compounds with an accuracy of 82.8%. Compound 4 was found to be a potent and selective inhibitor, with a relatively low IC(50) value. The binding mechanism of this compound was also investigated through molecular docking studies.
authors.affiliation: R&D Center, Youai Co., Ltd, Gyeonggi Bio-Center, Suwon, Gyeonggi-do 443-766, South Korea.
authors.forename: Ky-Youb
authors.initials: KY
authors.lastname: Nam
authors.forename: Nam Song
authors.initials: NS
authors.lastname: Choi
authors.forename: Cheol Kyu
authors.initials: CK
authors.lastname: Han
authors.forename: Soon Kil
authors.initials: SK
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002417:Cattle; D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D058986:Phosphodiesterase 5 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D012680:Sensitivity and Specificity; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D047188:Chalcones; D007527:Isoenzymes; D058986:Phosphodiesterase 5 Inhibitors; D054852:Small Molecule Libraries; D014665:Vasodilator Agents; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human