Synthesis And Evaluation Of The Antibacterial Activities Of Dihydrogen Triazine Derivatives

Bacterial infection is one of the most common diseases which could cause 5000 deaths one day in people's life.Over 2 million people deaths cases of the increasing of drug-resistance bacteria and worsening of the disease which threatening humans'health seriously-Many kinds of chemical synthetic drugs using in clinical trial including antibiotics,sulfonamides,imidazoles nitroimidazoles,quinolones,but almost all of them have clinical drug-resistance.So,developed antibacterial drugs could no longer meet our needs at the present stage.We must be compensated for this by exploiting new drugs constantly.Therefore,focus on developing new drug against multi-resistance bacteria is very important.Depending on the literature,we found that triazine ring has a variety of biological activities such as hypoglycemic,anti-tumor,antibacteria.In previous studies,we found that chalcone,phenoxy acetophenone,naphthoxyl acetophenone,benzyl benzene and benzyl naphthalene showed a good antibacterial activity.Based on the combination principle,A,B,C,D and E as a lead compounds,we designed and synthesized five series of dihydrogen triazine derivatives including 13a-i,14a-b,15a-c,16a-b and 17a-h.The compounds in all five series were screened for their in vitro antibacterial activities with MICs value in the range of 0.5-64 ?g/mL which against several Gram-positive bacterial strains(S.Aureus 4220,QRSA CCARM 3505,MRSA CCARM 3 167,Streptococcus mutans 3289)and gram-negative bacterial strains(E.coli 1924,P.Aeruginosa 2742,S.Typhinurium 2421)and fungus(Candida albicans 7535),.17e,17g and 17h exhibited strong antibacterial activity against four Gram-positives and a Gram-negative(E.coli 1924)with MICs value of 0.5 or 1?g/mL.Compounds 17e,17g and 17h did not affect cell viability on the Human liver cells at their MICs(1 or 0.5 mg/mL,respectively)but showed cytotoxicity at much higher concentrations.The 17h showed the most potential activity in Gram-positive bacterial strain test,which antibacterial spectrum was similar to Gatifloxacin and Moxifloxacin as the positive control drugs.Especially for QRSA CCARM 3505,17h(MIC=0.5 ?g/mL)showed 8-and 16-fold higher activity than moxifloxacin(MIC=4 ?g/mL)and gatifloxacin(MIC=8 pg/mL)as the reference drug.The 17h(MIC=0.5 ?g/mL)showed good antibacterial activity against E.coli 1924 in Gram-negative strain test,which was 4-fold higher activity than moxifloxacin(MIC=2 ?g/mL)and gatifloxacin(MIC=2?g/mL)as the reference drug,but it was ineffective to P.Aeruginosa 2742,S.Typhinurium 2421 among these Gram-negative strains.