探索抗生素的本质（英文PPT）Probing Nature for Antibiotics.ppt
Probing Nature for AntibioticsStruggle for ,www.photos-screensaver-,www.creswell-crags.org.uk n“History of humankind can be regarded from a medicinal point of view as a struggle against infectious diseases”Yoneyama,H.,Katsumata,R.,Biosci.Biotechnol.Biochem.,2006,70,1060Survival against infectious diseasesdodd.cmcvellore.ac.in, What are antibiotics?Molecules that stop the microbial growth(both bacteria and fungi)or kill them outright Walsh,C.,Antibiotics Actions origins and Resistance,2003,4How do the antibiotics act against bacteria?Walsh,C.,Antibiotics Actions origins and Resistance,2003, Cell Wall Biosynthesis -lactams,Cyclosporins,GlycopeptidesHow do the antibiotics act against bacteria?Walsh,C.,Antibiotics Actions origins and Resistance,2003,19 Protein BiosynthesisAminoglycosides,Macrolides,Tetracyclines,OxazolidinonesHow do the antibiotics act against bacteria?Walsh,C.,Antibiotics Actions origins and Resistance,2003,19 publications.nigms.nih.gov, DNA BiosynthesisQuinolonesRNA BiosynthesisRifampicinHow do the antibiotics act against bacteria?Walsh,C.,Antibiotics Actions origins and Resistance,2003,19 Metabolic pathways Folic Acid MetabolismTrimethoprim,SulfonamidesFatty Acid BiosynthesisTriclosan,Isoniazid,EthionamideWhy do we need more antibiotics?-Developing antimicrobial resistanceBacterial species Common types of Antimicrobial Types of Infections ResistanceStreptococcus pneumoniae-lactams,cephalosporins,macrolidesOtitis media,pneumonia,Tetracyclines sinusitis,meningitis Staphylococcus aureusCommunity-associated Meticillin,cephalosporins,macrolides Skin,soft tissue,sepsis pneumoniaHealthcare-associated Meticillin,cephalosporins,quinolones,Endocarditis,pneumonia,aminoglycosides,macrolidessepsisEnterococcus spp.Ampicillin,vancomycin,aminoglycosides Sepsis,urinary tract Furuya,E.Y.,Lowy,F.D.,Nature,2006,4,36What should be targeted?The compounds with,nNovel structuresnNew modes of actionFernandes,P.,Nature Biotechnology,2006,24,1497Where do the antibiotics come from?NATUREWhere do the antibiotics come from?NATURENPSSTSWhere do the antibiotics come from?NATURENPSSTSHelps in designing the moleculesNatural products as antibioticsnNaturally occurring compounds that are end products of secondary metabolism.nMostly extracted from plants,marine organisms,or microorganisms.Singh,S.B.,Barrett,J.F.,Biochemical Pharmacology,2006,71,1006Natural products as antibioticsnNaturally occurring compounds that are end products of secondary metabolism.nMostly extracted from plants,marine organisms,or microorganisms.nEg:Singh,S.B.,Barrett,J.F.,Biochemical Pharmacology,2006,71,1006Pal,S.,Tetrahedron,2006,62,3171ErythromycinIsolation-Streptomyces erythreus in 1952Uses -Respiratory tract diseases,genital infectionsMOA -Inhibition of protein synthesis Antibiotics which are semi-synthesizednSynthetically modified chemical compounds which are originated from natural products.Walsh,C.,Antibiotics Actions origins and Resistance,2003,4 Erythromycin isAcid unstablePal,S.,Tetrahedron,2006,62,3171Antibiotics which are semi-synthesizedClarithromycinAzithromycinHMR3647TE802Pal,S.,Tetrahedron,2006,62,3171Antibiotics which are totally from synthesisnTotally synthesized molecules which are potent as antibiotics.nThree main types.1.Sulfa drugs 2.Quinolones 3.OxazolidinonesSingh,S.B.,Barrett,J.F.,Biochemical Pharmacology,2006,71,1006Antibiotics which are totally from synthesisnSulfa drugs(Sulphonamides)Uses -Urinary tract infections,pneumonia etc.MOA -Inhibition of folate synthesis Harold,P.L.,OGrady,F.W.,Antibiotic and Chemotherapy,1992,6,268-272SulfamethoxazoleSingh,S.B.,Barrett,J.F.,Biochemical Pharmacology,2006,71,1006Antibiotics which are totally from synthesisnSulfa drugs(Sulphonamides)Naturally occurringUses -Urinary tract infections,pneumonia etc.MOA -Inhibition of folic acid biosynthesis Harold,P.L.,OGrady,F.W.,Antibiotic and Chemotherapy,1992,6,268-272SulfamethoxazoleSingh,S.B.,Barrett,J.F.,Biochemical Pharmacology,2006,71,1006Walsh,C.,Antibiotics Actions origins and Resistance,2003,80-82p-aminobenzoic acidAntibiotics which are totally from synthesisnQuinolones CiprofloxacinUses -Urinary tract infections,Lower respiratory infections,Gastrointestinal infectionsMOA -Inhibition of DNA synthesis Singh,S.B.,Barrett,J.F.,Biochemical Pharmacology,2006,71,1006Antibiotics which are totally from synthesisnQuinolones Naturally occurringCiprofloxacinUses -Urinary tract infections,Lower respiratory infections,Gastrointestinal infectionsMOA -Inhibition of DNA synthesis Singh,S.B.,Barrett,J.F.,Biochemical Pharmacology,2006,71,1006Kunze,B.,Hofle,G.,Reichenbach,H.,J.Antibiotics,1987,40,258Aurachin CAurachin DAntibiotics which are totally from synthesisnOxazolidinones Ford,C.W.,Zurenko,G.E.,Barbachyn,M.R.,Current Drug Targets-Infectious Disorders,2001,1,181LinezolidUses -Soft tissue infections,skin infections,Tuberculosis etc.MOA -Inhibition of protein synthesis Antibiotics which are totally from synthesisnOxazolidinones Naturally occurringFord,C.W.,
