Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5

The traditional Chinese medicines (TCM), Epimedium sagittatum (ESs), Cnidium monnieri (CMs), and Semen cuscutae (SCs), were used for treating erectile dysfunction since the ancient Han dynasty (202 BC–AD 220). Phosphodiesterase-5 (PDE-5) is deemed the target protein for inhibition to treat erectile dysfunction. In this study, a reliable multiple linear regression (MLR) model (r value = 0.8484) was used to predict the activities of new candidates which were designed from ES, CM, and SC. From docking and pharmacophore analysis, the potent candidates among ES, CM, and SC were screened. SC01, SC03, and ES03b were predicted to have high potencies based on MLR analysis and high docking scores. Additionally, from our analysis, we make the follow conclusion (1) Hydrophobic compounds tend to be more potent PDE-5 inhibitors; (2) Because of the big binding site, inhibitors with molecular weights over 500 remain potent; (3) From the pharmacophore analysis, the features of hydrogen bond acceptors are the basis for designing novel inhibitors of PDE-5 and (4) According to MLR analysis, the number of ring groups could be up to 6, but the number of aromatic rings was limited to 4 to be potent. This study offers an alternative way to screen PDE-5 inhibitors from TCM and provides a scientific basis for confirming pharmacological actions of TCM.