Synthesis And Bioactivity Evaluation Of Jaspine B Analogues And Cationic Antibacterial Peptides Mimics

Jaspine B is a natural product extracted from marine organism sponges with significant antitumor activity.Studies have shown that it can inhibit the proliferation of various tumor cells at a concentration of 0.01 ?g/mL.According to the structure of jaspine B,we have designed and synthesized 14 jaspine B analogues bearing a 2-tetradecylaminomethyl group.The cytotoxicity of these compounds was evaluated by MTT assay,Compound 2-3f and 2-3g have a better activity against PC-3 and MCF-7 cell lines,IC50 values were 0.859 ?M and 0.719 ?M,respectively.Preliminary study on the mechanism of compound 2-3f on prostate cancer cell line PC-3,flow cytometry was used to assess the extent of cell apoptosis,the result shows that compound 2-3f could not induce the early apoptosis of tumor cells;Western blot assay demonstrates compound 2-3f could cause changes in the expression of autophagy marker protein;Mitochondrial membrane potential assay proves compound 2-3f could decrease the mitochondrial membrane potential;LC3 protein fluorescence confocal microscopy assay indicates compound 2-3f could increase the the expression of LC3 protein.The above results show that the mechanism of compound 2-3f is to induce autophagy in tumor cells.2.Antibacterial peptide is a highly effective antimicrobial spectrum is not easy to produce drug resistance of the new antibiotics,the aim of designing and synthesizing small molecule cationic antimicrobial peptidomimetics is to develop new antibacterial candidate drugs.On the basis of previous work in our laboratory,Twenty-six small molecular cationic antimicrobial peptides were synthesized by introducing triazole and tested for their minimum inhibitory concentration against four sensitive strain,compound 3-5g,3-5h,3-5i,3-5y and 3-5z had high antibacterial activity.Then the minimum inhibitory concentration of the five compounds was tested against four different resistant strains,all of them possessed good antibacterial activity.Erythrocyte hemolysis assay showed compound 3-5z was good at lower erythrocyte toxicity.In addition,compound 3-5z was proved that it was stable in plasma by testing its minimum bactericidal concentration(MBC),the MBC was only double after it was treated with plasma six hours.