Abstract:
Lipoxygenase -5 (5-LOX), as one of the key enzymes for leukotriene synthesis, is an important target in the study of inflammatory response. At present, most of the related marketed drugs have the disadvantages of hepatotoxicity and short half-life, so it is necessary to develop and study the 5-LOX inhibitor with low hepatotoxicity and high inhibitory activity. Based on the previous studies, it was found that the lignans in the traditional medicinal resource
Litsea plants might have certain 5-LOX inhibitory activity. Therefore, de novo evolution, drug-like rule and ADMET screening and other computer-aided drug design techniques were adopted for in-depth study. It is found that all the molecules grown from de novo design fragments have good screening results. Among them, 11 small molecules had higher molecular docking scores and their residue binding patterns were similar to zileuton’s. In particular, they had the advantages of low hepatotoxicity and low plasma protein binding rate. The results showed that the 11 small molecules obtained by de novo design of lignan compounds in
Litsea plants had certain potential 5-LOX inhibitory activity, and had the advantages of low hepatotoxicity and low plasma protein binding rate, which had certain in-depth research value. And through the analysis of the interaction of residues, it provided some reference for the follow-up research.