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

Erectile 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 α-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 α-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.