Comparison of PDE-5 inhibitors used in erectile dysfunction with some candidate molecules: A study involving molecular docking, ADMET, DFT, biological target, and activity

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dc.contributor.authorSagir, Suleyman
dc.contributor.authorUnsal, Velid
dc.contributor.authorOner, Erkan
dc.contributor.authorYildiz, Resit
dc.contributor.authorMert, Basak Dogru
dc.date.accessioned2025-04-09T12:32:04Z
dc.date.available2025-04-09T12:32:04Z
dc.date.issued2025
dc.description.abstractErectile dysfunction (ED) is a urological condition defined as the inability of a man to achieve or maintain an erection. This condition negatively affects his sexual performance and the performance of his partner. Phosphodiesterase type 5 (PDE5) inhibitors are commonly used to treat ED. Arginase II plays an important role in regulating L-arginine to NO synthase in the smooth muscle of the human corpus cavernosum of the penis. NO is a molecule essential for regulating a variety of functions, including arterial blood pressure, penile erection, and energy balance. Substances such as vardenafil, alprostadil, papaverine, and resveratrol increase NO production, thereby supporting sexual function and vascular health. Additionally, NO donors such as L-arginine, L-citrulline, and alpha-lipoic acid provide effective alternatives when used in combination with PDE5 inhibitors. Medications used in the treatment of ED include vardenafil, alprostadil, and papaverine. In addition, although molecules such as L-arginine, citrulline, resveratrol, alpha-lipoic acid, and rutin are thought to play a role in ED, their pharmacological and molecular effects have not been sufficiently elucidated. The aim of this study was to investigate the effects of these molecules in the treatment of ED by computer-based calculations, to obtain new information about them and to inspire new treatment strategies for ED. The physicochemical, molecular and pharmacokinetic properties of the compounds were determined by SwissADME software, and ADMET (absorption, distribution, metabolism, excretion and toxicity) data were determined by ADMETlab 3.0 software. Biological target and activity data were obtained by MolPredictX and PASS Online software. While the Gaussian 09 program was used for DFT calculations, PyMOL, AutodockTools 4.2.6, AutoDock Vina, and Biovia Discovery programs were used for molecular docking studies. It was found that L-arginine, citrulline, resveratrol and alpha-lipoic acid were well absorbed from the intestine, while rutin showed limited absorption. When their metabolic risks were evaluated, L-arginine and citrulline were found to have lower toxicity. Molecular docking results of rutin and resveratrol were remarkable. The electronic properties of the compounds were explained by DFT calculations. L-arginine and citrulline were found to have low toxicity and positive therapeutic effects. L-arginine and citrulline stand out as promising candidates for future research. Although resveratrol data are promising, unfortunately their potential toxicity and metabolic interactions require further investigation. It is important to learn more about these compounds or conduct research to improve their therapeutic efficacy. Although computer-based calculations play an important role in toxicity predictions, drug interactions, pharmacokinetics and toxicity properties should be carefully evaluated.
dc.identifier.doi10.1186/s12894-025-01727-5
dc.identifier.issn1471-2490
dc.identifier.issue1
dc.identifier.trdizinid40069715
dc.identifier.urihttp://dx.doi.org/10.1186/s12894-025-01727-5
dc.identifier.urihttps://hdl.handle.net/20.500.14669/4291
dc.identifier.volume25
dc.identifier.wosWOS:001441785100001
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherBMC
dc.relation.ispartofBmc Urology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20250362
dc.subjectErectile dysfunction
dc.subjectPDE-5 inhibitors
dc.subjectNOS
dc.subjectArginase II
dc.subjectADMET
dc.subjectMolecular docking
dc.titleComparison of PDE-5 inhibitors used in erectile dysfunction with some candidate molecules: A study involving molecular docking, ADMET, DFT, biological target, and activity
dc.typeArticle

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