Peptide Off The Design And Synthesis Of Carbamoyl Enzyme Inhibitors

The emergence of multi-drug resistant bacterial has created an urgent demand for new antibacterial agents with novel mechanisms of action and new stractures. One of the new targets currently receiving widespread interest is peptide deformylase (PDF). Now, the infection is so massive that it is a new challenge for pharmacognosists to elongate the availability life of the current antibiotics and find new drug targets to design novel antibiotics.One of the most important mechanisms of antibiotics to kill bacteria is to inhibit some links of metabolism or some enzymatic system in microbes. If some antibiotics are able to inhibit some common metabolic pathway of microbes, such as the synthesis of protein and nucleic acid, they will inhibit the growth of many kinds of bacteria to achieve the purpose of broad-spectrum antibiosis.Peptide deformylase, a kind of enzyme, is essential in protein synthesis in bacteria, while it is not necessary in mammalian cells. The inhibitors of PDF show broad-spectrum antibacterial activity and good selectivity. So, PDF has become a new antibacterial drug target in recent years.Among many PDF inhibitors, actinonin is a good natural PDF inhibitor and has certain antibacterial activity outside bodies but no activity inside bodies for the bioavailability. Therefore, there is big development space to use actinonin as leading compound to design and synthesize novel PDF inhibitors.According to the structure-activity relationships of actinonin and the theory that drug binds with acceptor, we use the actinonin as leading compound to synthesize some series of hydroxamic acid derivatives and N-formylhydroxylamine derivatives containing benzimidazole.