The Structure Design,Synthesis And Bioactivity Of The Platensimycin Derivatives Based On Fab/f Enzyme

Platensimycin have remarkable in antibacterial activity for its unique structure which containing two active site which carboxyl groups and four ring skeleton structure,and it has an important role in anti-gram-positive resistant bacteria activty.In this paper,the structure of platensimycin was modified for its four ring skeleton structures,which benzene ring groups with electrons withdrawing and electrons donating groups as well as schiff base groups taking part in constructing new platensimycin derivatives.In this paper,the nine platensimycin derivatives were characterized by NMR,MS and IR,And their antibacterial and anticancer activities were studied.1.The experiment explore the relationship between the nine derivatives of platensimycin and antibacterial activity.by using the paper agar diffusion methord.It has found that the three derivatives of platensimycin A6,A7,A8 were sensitive to Staphylococcus aureus and they have antibacterial activity in the screening experiment of standard bacterias;and A9 was sensitive to E.coli and it has antibacterial activity.As well as,it has found that the value of FICI between 1.031 and 1.063 in A6 combined with ceftriaxone sodium and He ikari cephalosporin,moreover,it show independent action in the chessboard dilution method.In the same way,the value of FICI between 0.281 and 1.063 in A7 combined with ceftriaxone sodium and He ikari cephalosporin,moreover,it show synergistic effect..In vitro anti-resistance activity experiment,it has found that the value of MIC is 64-512μg/ml and MBC is 64-512μg/ml in A6,A7,A8 for MRSA and other bacteria were isolated in eight strains of clinical bacteria.2.Anticancer activity of nine platensimycin derivatives were evaluated.The tests showed that A8 and A9 compound which have medium anticancer activity in cancer cells HCT116.3.The interaction of the four derivatives of platensimycin A6,A7,A8,A9 with FabF were studied by molercular docking methord.The results suggested that some amino acid residues of FabF interact effectively with platensimycin derivatives.