• Save
Aminoglycosides(medicinal chemistry by p.ravisankar)
Upcoming SlideShare
Loading in...5
×
 

Aminoglycosides(medicinal chemistry by p.ravisankar)

on

  • 2,585 views

Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its ...

Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its importance,therapeutic uses, toxicity.

Statistics

Views

Total Views
2,585
Views on SlideShare
2,585
Embed Views
0

Actions

Likes
2
Downloads
0
Comments
0

0 Embeds 0

No embeds

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Aminoglycosides(medicinal chemistry by p.ravisankar) Aminoglycosides(medicinal chemistry by p.ravisankar) Presentation Transcript

    • AMINOGLYCOSIDES(MEDICINAL CHEMISTRY)Prof.P.RavisankarVignan Pharmacy CollegeVadlamudiGuntur (Dist)Andhra Pradesh, India.banuman35@gmail.comPhone: 0905999400009000199106
    • Amino glycoside antibiotics contain an amino cyclitol moiety towhich aminosugars are linked glycosidically.They may be more correctly called aminocyclitol antibiotics.Aminoglycosides are a group of antibiotics effictive against gram+ve andgram-ve organismsas well as micoplasma .Most of the aminoglycosides antibiotics are dirived from genus streptomycesspecies, important one is streptomycin.Aminoglycoside antibiotics are also referred as aminocyclitol antibiotics,because they consist of a highly substituted ring called aminocyclitol ring i.e.1,3 di amino cyclohexane central ring.(pharmacophoric 1,3-diaminoinositol moiety consisting of eitherstreptamine,2-deoxystreptamine(Or) spectinamine.)Streptidine = streptomycinNeomycinGentamycinkanamycinTobramycinAll aminoglycosides in this class possess one amino hexose sugar.butsome antibiotics likeStreptomycin,neomycin,paramomycin possess a pentonse sugar.Due to several amino groups aminoglycosides are basic in nature.Deoxy streptamine(Aminocyclitols)The chemistry,spectrum,potency,toxicity,And pharmacokinetics of these agentsare a function of the specific identityof the diaminoinositol unit and thearrangement and identity of theattachments.
    • Aminocyclitols??? Cyclohexanes with several substituted orunsubstituted amino and hydroxyl groups whichbring them high water solubility. Streptidine and Streptamine can be called 1,3-diguanidino and 1,3-diamino inositol, respectively.1,3 Diaminoinositol moieties inaminoglycosides
    • General characteristics of amino glycosides Amino glycosides are polycations and are highlypolar they are water soluble. They are basic and form salts with acids. They are poorly absorbed after oral administrationthat’s why they do well when given parentally. Because aminoglycosides are quickly broken downin the stomach, these antibiotics cant be givenorally, but instead must be injected. Aminoglycosides can cross the placental barrier. They are unable to cross blood brain barrier sothey can’t be used for the treatment of meningitisunless they are injected directly in to the CNS.
    • In the 1940’s soil actinomycetes bacteria were systematicallyscreened for the elaboration of antimicrobial substances
    • Streptomycinisolated in 1943 from Streptomyces griseus-6 membered ring with 2 glycosylated aminosugars- cationic compoundClassified as an Aminoglycoside.
    • StreptomycinLarge scale productionWent into play in the1950’sMajor break throughIn the treatment ofTuberculosis
    • STYPTOMYCIN(STN) Streptomycin is the first aminoglycoside antibiotic which wasisolated from the actinomycetes bacteria Streptomyces griseusand several related soil microorganisms. Streptomycin was first discovered in 1943 by Selman abrahamwakesman and received a Nobel prize in 1952.It was introduced in 1943 primarily for the treatment oftuberculosis.Chemistry of streptomycin:Streptomycin is a triacidic base and has an aldose sugar.It is a water soluble with basic properties.The hydrophilic nature of streptomcin results in very poor absorptionfrom GIT.The two guanidino groups attached to the streptidine exhibitsstrong basic nature.The amino sugars attached to streptidine by means ofglycosidic linkages.
    •  The methyl amino group attach to N-methyl-L-glucosamine exhibitsweakly basic natue. Streptomycin is made up of 3 basic structural units called ….Streptidine(a diguanidino compound)Streptose (a aldose sugar)N-methyl-L-glucosamine unit.Physico- chemical properties:Colour: colourless.Odour : odourless.State : Streptomycin sulphate andstreptomycin chloride available in the form of whitepowdery solid.Solubility : Easily soluble in water insoluble in acetone.Stability: It is stable at a temp. less than 280c andsolutions of streptomycin are stable at pH (4.5-7).
    • StreptobiosamineWeakly basicStreptomycin is made upOf 3 basic structural unitsCalled…1. Streptidine(adiguanidinocompound)2. Streptose (a addose sugar)3. N-methyl-L-glucosamine.
    • SAR of streptomycin Modification of α-streptose portion of streptomycin has beenextensively studied.1. Reduction of aldehyde to alcohol results in a compounddihyrostreptomycin activity is similar to streptomycin but producingsevere deafness.2. Oxidation of aldehyde group to a(oxime,semicarbazone,phenylhydrazone) Schiff basederivatives results in inactive analogues.3. Oxidation of –CH3 group in α-streptose to a methylene hydroxygives an active analogous but has no advantage over STM.4. Modification of amino methyl group in the glucosamine bydemethylation and replace by larger alkyl groups reduces activity.5. In N-methyl-L-glucosamine( –NHCH3 group) is very essential for theacivity.6. Guanidino groups streptidine ring are essential .Replacement ofguanidino groups reduces the antibacterial activity.7. In N-methyl –L-glucosamine the “N” atom should be secondaryamine.
    • DIHYDROSTREPTOMYCINThe only difference in the structure of streptomycin and dihydrostreptomycin is thePresence of a hydroxyl alcoholic group(-CH20H) in place of –CHO group ofStreptose moiety. the –CHO group of streptomycin is replaced by –CH2OH group)It is a semisynthetic derivative obtained by the catalytic hydrogenation ofStreptomycin.It is formed by the hydrogenation of aldehydic carbonyl group of the streptose moietyPresent in streptomycin to a primary alcohol.Infact it is more stable than streptomycin.It has similar mechanism of action, pharmacokinetic aspects and toxicological propertiesas that of streptomycin.It has generally fewer side effects than streptomycin but it has a higher risk ofOtotoxicity than streptomycin.Spectrum of activity:It shows broad spectrum of activity in the treatment of systemic infections caused byGram-ve mo’s Brucella,Haemophilus,shigella,Klebsiella,pasteurella and most effectiveAgainst Mycobacterium tuberculi.Toxic effects/adverse effects:Ototocicity,Nephrotoxicity,Neuromuscular paralysis and allergic reactions.IMPORTANCE OF DIHYDROSTREPTOMYCIN:Treatment of tuberculosis in various animals.It is less neurotoxic than streptomycin but high frequency of ototoxicity in humans.Dihydrostreptomycin is used in combination with procaine penicillin to treat systemic infectionsIt is not recommended for humans as it is ototoxic and hence mostly used for veterinarypurposes for the treatment of systemic infections.The therapeutic dose in animals is 11mg/kg body weight given through IM route.
    •  Penicillin G procaine ------ 200,000/IUDihydrostreptomycin sulphate-------- 200,000/IUThe combination of penicillin G procaine anddihydrostreptomycin acts additive and in somecases synergistic.Procaine penicillin G is a small-spectrum penicillinwith a bactericidal action against mainly Gram-positive bacteria like Campylobacter, Clostridium,Corynebacterium, Erysipelothrix, Haemophilus,Listeria, penicillinase negative Staphylococcus andStreptococcus spp.INDICATIONSArthritis, mastitis and gastrointestinal, respiratoryand urinary tract infection caused by penicillin anddihydrostreptomycin sensitive micro-organisms,like Campylobacter, Clostridium, Corynebacterium,E.coli, Erysipelothrix, Haemophllus, Klebsiolla,Listeria, Pasteurella, Salmonella, andStaphylococcus spp., in calves, cattle, goats, sheepand swine. Infections due to susceptible organisms, respiratory, reproductive and urinary tract infections, pre- and post- operative prophylaxis, mycotic dermatitis, abscess,inflammation andallergic conditions in cattle,horses,cows,gots,pigs,sheeps.DihydrostreptomycinAlone used mainlyagainstE.coli,Klebsiella,Pasteurella,Salmonella,Strephylococcus.
    •  Dihydro streptomycin +penicillin combination is currently usedas broad-spectrum antibiotics for the treatment of infections dueto a wide range of Gram-positive and Gram-negative bacteria.These include foot abscess. osteomyelitis, peritonitis, septicaemia, scours, pneumonia,cystitis, peracute mastitis. post-operative prophylaxis, metritis, bacterial enteritis,leptospirosis. actinomycosis/actinobacillosis and respiratory, reproductiveand urinary tract infections. They are also widely used in footrot eradication and controlprograms. dihydro) streptomycin only products for use in cattle, sheep,pigs orpoultry. prophylactic leptospirosis treatment of cattle for live export(Leptospirosis is a zoonotic disease with serious human healthimplications )
    • Dihydrostreptomycin:OHCIt is an antibiotic consistingof hydrogenated form ofStreptomycin.Aldehyde (-CHO)groupof streptose moietyis replaced by-CH2OH group.
    • Streptamine.(Diaminocompound)
    • Mechanism of Action1. Ionic binding to outer membrane lipopolysaccharides & proteins2. Disruption of cell membrane permeability- Displace Ca and Mg- Transient hole formation in the cell membrane- Uptake of the aminoglycoside through the holes3. Binding to 30 S ribosomal subunit- Interfere with translational accuracy leading to miscoding- Decrease in protein synthesis
    • Mechanism of Action of Aminoglycosides Inhibition of protein biosynthesis initiationupon attachment to 30s portion ofribosomes. Misreading mutation of the genetic codeand the synthesis of nonesense proteinswhich are not normal proteins so theycannot take part in cellular activities. Nonesense proteins disturb thesemipermeability of the bacterial cell andaminoglycoside molecules enter the celleasily and kill it.
    • Mechanisms of action Aminoglycosides have several potential antibiotic mechanisms, some asprotein synthesis inhibitors, although their exact mechanism of action isnot fully known: They interfere with the proofreading process, causing increased rateof error in synthesis with premature termination. Also, there is evidence of inhibition of ribosomal translocation wherethe peptidyl-tRNA moves from the A-site to the P-site They can also disrupt the integrity of bacterial cell membrane. Depending on their concentration they act as bactereostatic orbactericidal agents. The protein synthesis inhibition of aminoglycosides does not usually producea bactericidal effect. Recent experimental studies show that the initial site of action is theouter bacterial membrane. The cationic antibiotic molecules create fissures in the outer cellmembrane, resulting in leakage of intracellular contents andenhanced antibiotic uptake. This rapid action at the outer membraneprobably accounts for most of the bactericidal activity. Aminoglycosides competitively displace cell biofilm-associated Mg2+ andCa2+ that link the polysaccharides of adjacent lipopolysaccharide molecules."The result is shedding of cell membrane blebs, with formation of transientholes in the cell wall and disruption of the normal permeability of thecell wall. This action alone may be sufficient to kill most susceptible Gram-negative bacteria before the aminoglycoside has a chance to reach the 30Sribosome
    • (Chloram-Phenicolblockshere)AminoglycosidesBlocks translocation
    • Freeze initiationBlock peptidebond formationMisreading of mRNAp-Site(Peptidyl site)on which thet-RNA holds theElongated peptide chain.(A-site)Amino acetylt-RNA bindingsite.(attachment ofIncomming aminoAcid by t-RNA.(Aminoglycosidesblocks translocationhere)ChloramphenicalBlocks transpeptidation
    • Therapeutic uses of aminoglcosides: The most frequent use of aminoglycosides is empiric therapy for serious infections such assepticaemia. complicated intraabdominal infections complicated urinary tract infections, respiratory tract infections.Energy is needed for aminoglycoside uptake into the bacterial cell Anaerobes have less energy available for this uptake, so aminoglycosides are less activeagainst anaerobes . Aminoglycosides are useful primarily in infections involving bacteria,such aerobic gram –ve Pseudomonas Actinobacter and Enterobacter In addition, some Mycobacteria, including the bacteria that cause tuberculosis, aresusceptible to aminoglycosides. Streptomycin was the first effective drug in the treatment of tuberculosis In the past the aminoglycosides have been used in conjunction with beta-lactamantibiotics in streptococcal infections for their synergistic effects, particularly inenocarditis. One of the most frequent combinations is ampicillin (a beta-lactam, or penicillin-relatedantibiotic) and gentamicin. Often, hospital staff refer to this combination as "amp and gent" or more recently called"pen and gent" for penicillin and gentamicin. Experimentation with aminoglycosides as a treatment of cystic fibrosis (CF). Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi, and viruses. frequent occurrence of nephrotoxicity and ototoxicity during aminoglycoside treatmentmakes physicians reluctant to use these compounds in everyday practice although more research still needs to be done in order to overcome this problem entirely.
    • Aminoglycosides toxicity Answer Nephrotoxicity Ototoxicity Neuromuscular paralysis.
    • Toxicity/Adverse effectsAll aminoglycosides are ototoxic and nephrotoxic.Ototoxicity and nephrotoxicity are more likely to be encountered whentherapy is continued for more than 5 days, at higher doses, in the elderly,and in the setting of renal insufficiency.Concurrent use with loop diuretics (eg, furosemide, ethacrynicacid) or other nephrotoxic antimicrobial agents (vancomycin,amphotericin) can potentiate nephro-toxicity and should be avoided.Ototoxicity can manifest as auditory damage, resultingin tinnitus and high-frequency hearing loss initially,or as vestibular damage, evident by vertigo, ataxia,and loss of balance.
    • Streptomycin and gentamicin are the most vestibulotoxic.Nephrotoxicity results in rising serum creatinine levels or reducedcreatinine clearance.Neomycin, kanamycin, and amikacin are the mostototoxic agents.Neomycin, tobramycin, and gentamicin are the most nephrotoxic.In very high doses, aminoglycosides can produce a curare-like effectwith neuromuscular blockade that results in respiratory paralysis. Thisparalysis is usually reversible by calcium gluconate(given promptly) or neostigmine.Hypersensitivity occurs infrequently.
    •  OTOTOXICITY: Progressively damage the sensory cells of the cochlea and vestibular apparatus Killed sensory cells do not regenerate Loss of hearing, vertigo, ataxia, and loss of balanceVistibular toxicity: Nausea, vomiting, cold sweats Vertigo Aaxia Nystagmus.Cochlear damage: Varying degrees of hearing loss High frequency tones Tinnitus Sense of fullness or aching in the ears.
    •  Vestibular damage gentamycin and streptomycin Cochlear damage kanamycin, amikacin, and neomycin Streptomycin  deafness Equally affect Tobramycin.How to avoid ototoxicity: Renal, auditory, and vestibular function- assessed before, during, and following therapy Aminoglycoside serum concentrations Avoiding prolonged therapy and ototoxic agents Maintain hydration, urine output, and normal serum electrolytes Recommend : stop the aminoglycoside at the first sign of
    • Nephrotoxicity: Pathophysiology More polycationic like gentamicin and neomycin, enter proximal tubular cells bypinocytosis. Inhibit lysosomal enzymes, the vesicles accumulate ( cytosegresomes ) Excessive numbers of these apparently kill the cells, producing severetoxicity. Proximal tubular necrosis, may not see clinically Acute nonoliguric renal failure Proximal tubular damage causes the whole nephron to fail  increased serum aminoglycoside concentrations. Proximal renal tubular cells regenerate Nephrotoxicity is not limited to proximal tubular toxicity but also may involve the medullar region (Henle loop andcollecting duct) of the nephron.
    • Risk factors: Advanced age Sepsis, Shock Prolonged aminoglycoside usage Underlying renal insufficiency Coadministration of other nephrotoxic agents Dehydration Decreased albumin or poor nutritional status Pneumonia Hypercalcemia Leukemia Rapidly fatal illness Liver or kidney disease Pleural effusion, ascites Reduced aminoglycoside clearance Elevated initial steady-state concentration
    •  Which one is the most dangerous?• Based on dose-response data• Gentamicin > Tobramycin & amikacin > Netilmicin•Number of free amino groups & relative nephrotoxicity.How to treat? Supportive Discontinuation DialysisHow to minimize nephrotoxicity?Renal function tests Serum creatinine levels Abnormal urinary sediment Leukocyturia Elevated levels of beta-2 microglobulins excreted in the urine Once-daily Dose
    • Neuromuscular paralysis Inhibit Ca++into nerve on depolarization required for exocytotic ACh release Ca++injections can improve release Weakness at doses on top end of range if any renal problem Respiratory paralysis if use for lavage of peritoneal or pleural cavity.To prevent all these side effects: Not Using Aminiglycoside !! There are antibiotics with equal or better sensitivity profilesthan aminoglycosides against GNRs and Pseudomonas. Once Daily Dose !! Nephrotoxicity Monitoring !!
    • CHLORAMPHENICOL (chloromycetin) Chloramphenicol was originally derived from the bacterium Streptomycesvenezuelae, isolated by David Gottlieb, and introduced into clinicalpractice in 1949, under the trade name Chloromycetin. It was the first antibiotic to be manufactured synthetically on a largescale. Chloramphenicol is a broad-spectrum antibiotic that acts as abacteriostatic, but at higher concentrations can act as a bactericidal. A broad spectrum antibiotic which is a nitrobenzine derivativederived from dichloro aceticacid. Structure and chemical characteristics Chloramphenicol contains a nitrobenzene ring, an amide bond, and analcohol function. The presence of chlorides in biologically produced organic molecules isunusual. The nitrobenzene is relevant because it leads to the formation ofaromatic amines which may be carcinogenic. The amide is hydrolyzed by some resistant bacteria leading inactivation. The alcohol serves as a functional group facilitating the formation ofesters that improve chloramphenicols water solubility. Chloramphenicolbase has low water solubility and high lipid (in organic alcohols)solubility. Its palmitate ester is similar, but the succinate ester has highwater solubility.
    • 1. moecular formula is C11H12Cl2N2O52.Basic nucleus is P-nitrobenzene contains aside chain at p-position to –No2 group.3.Side chain contains one –OH group at “b”and one hydroxymethyl group at “a”.4. on the “a” carbon presence of 2,2-dichloro-acetamide moiety hence the side chain canalso be named as acyl amido propanediol.5. Stereochemistry of chloramphenicol existsin 2 pairs of enanteomers(optically activecompounds which are mirror images.6. I contains 2 chiral carbons .7. 4 enantiomers are possibe.one is D and L threo– (2 identical groupsare opposite sides of chiral carbons)Erythro ( 2 identical groups are on sameside of chiral carbon atom.out of 4 enatiomers D- Threo form showsbiological activity..* a*b
    • Mechanism of action: Chloramphenicol is bacteriostatic (that is, it stops bacterial growth). It is a protein synthesis inhibitor Chloramphenicol binds to the 50S subunit of ribosomes and appears toact by inhibiting the movement of ribosomes along mRNA,probablyinhibiting the peptidyl transferase reaction by which the peptide chain isextend.-----------------------------------------------------------------------------------Since it binds to the same region as macrolides,lincosamides these drugscan’t be used in combination.The nitrogroup and both alcohol groups is also important but can bereplaced by other electronegative groups.Bacteria with resistance to the drug contain an enzyme calledChloramphenicol acetyltransferase, which catalyses the acylation ofthe hydroxyl groups.
    • Chloramphenicolblocks transpeptidationand proteinsynthesis.
    • Synthesis of chloramphenicol(dichloro acetyl chloride)(nitrated with nitric-sulfuricacid mixture)Saponification removes theAcetate protecting groups.
    • 3-phenyl,2-nitro1,3 propane diol
    • Side effects of chloramphenicol Abdominal pain; Bloating; Blood disorders which may be serious;Diarrhoea; Fatigue; Fever; Headache; Nausea and vomiting;Newborn babies with immature liver function can get a serious side effectwhere the skin develops a grey colour and there is circulatory collapse(grey syndrome)Pins and needles (paraesthesia);RashSore throatStomach upsetTingling of the hands or feetUnusual bleeding or bruisingVision changes or eye painVisual disturbances Vomiting; This drug is quite toxic to bone marrow (supression of bonemarrow).Thenitro group is suspecdted to be responsible for this, although intestinalbacteria are capable of reducing this group to an amino group. aplastic anaemia Anorexia
    • Uses of chloramphenicol Chloramphenicol is an antibiotic used to treat a variety of bacterialinfections In some regions in the world chloramphenicol is the drug of the choice for the treatment of typhoid when more expensive drugs cannotbe afforded. It is also widely used against eye and ear infections. Meningitis,Anthrax,Brucellosis Burkholderia Infections (in cystic fibrosis patients, immunocompromised patients ) Chlamydial Infections Clostridium Infections Vibrio (InfectionsTreatment of cholera caused by Vibrio cholerae) Ehrlichiosis,Plague,Rat-bite Fever Rickettsial Infections, Haemophilus influenzae infection Chloramphenicol treats only bacterial eye infections. Chloramphenicolwill not work for other types of eye infections anti-infective ear preparations. Those bacteria sensitive to this drug include clostridium, chlamydia,, salmonella. Chloramphenicol has also shown activity against Mycoplasma.
    •  Drug Interactions or Contraindications Chloramphenicol is contraindicated if another drug can be usedinstead due to its potential to cause bone marrow depression. Not recommended for use with Tylan, azithromycin orerythromycin, as they may be antagonistic with chloramphenicol. Acetaminophen will elevate chloramphenicol levels. Chloramphenicol has the potential to antagonize bactericidalactivity of the penicillins and aminoglycosides. Rifampin may decrease serum chloramphenicol levels. Chloramphenicol is also not recommended to be given in pregnant or lactatinganimals due to its ability to cross the placenta and passed in breast milk. Adverse Reactions Avoid using if impaired hepatic or kidney function is present. Prolonged use mayresult in suprainfections. ENT: optic neuritis GI: diarrhea, disturbance of intestinal flora Hematologic: irreversible idiosyncratic aplastic anemia (identified in humans),dose-related bone marrow suppression with long term therapy (reversible oncedrug stopped) Hepatic: jaundice Other: anaphylaxis May falsely elevate urine glucose levels
    •  Spectrum of Antimicrobial Activity Aminoglycosides are broad-spectrum antibiotics effective in:1. Systemic Infections caused by aerobic G(-) bacillus(klebsiella, proteus, enterobacters).2. Tuberculosis, Brucellusis, Tularaemia and yersinia infections.3. Amoebic dysentery, shigellosis and salmonellosis.4. Pneumonia and urinary infections caused by Pseudomonaaeroginosa. G(+) and G(-) aerobic cocci except staphylococci andanaerobic bacteria are less susceptible.
    • Microbial Resistance againstAminoglycosides Resistant strains have emerged againststreptomycin, kanamycin and gentamycinin clinic. R factor is resposible for the production ofaminoglycoside deactivating enzymes:1) Acetyl transferases (AAC)2) Phosphotransferases (APH),3) Nucleotidyl transferases (ANT) These enzymes transfer to hydroxyl andamino groups of the drug.
    • Aminoglycoside Deactivating Enzymes AAC acetylates 3-NH2 of the ring II, and 2`, 6`- NH2 of thering I. APH phosphorylates 3`-OHof the ring I and 2``-OH of thering III. ANT adenylates 2``,4``-OH of the ring III and 4`-OH ofthe ring I.OOOOOHNH2OHH2NOHNH2H2NHOH2NHOOH1 23456124132535466IIIIIIANT-4ANT-4ANT-2, APH-2AAC- 6AAC- 2APH- 3AAC- 3Kanamycin B
    • NeomycinOOOOOOOHCH2OHH2NNH2HONH2HOHONH2HOHOH2NH2CR2 NH22-DeoxystreptamineNeosamine CNeosamine C123345612345612344 5 12D-RiboseNeomycin Isolated from cultures of Streptomyces fradiaalong with an antifungal subsance: Fradicin. Effective against GI and dermal infections.
    • Gentamicin Isolated from cultures of Micromonospora purpurea. The suffix “micin” denotes its origin. It is used against urinary infections caused by G(-) andpseudomona.OOOOHCNH2H2NOHNHH3CNH2HO1234512346512345 6Garosamine2-DeoxystreptamineGentamicin C1: R1=R2 = CH3Gentamicin C2: R1 = CH3 ; R2 = HGentamicin C1a: R1=R2 = HOHCH3NHR2R1Lacks 3`-OHAPH ResistantAxial and tertiary 4``-OH instead ofequatorial secondary 4``-OH in KanamycinANT ResistantSecondary amino group at 6`-NH2 inGentamycin C1, spacial hynderanceAAC ResisistantIIIIII
    • TobramycinIsolated from cultures of Streptomycestenebrarius.Antimicrobial activity against resistanceP.aeroginosa.OOOOH2CNH2H2NOHNH2HONH2HO2-DeoxystreptamineTobramycinHOH2CHO1123451543 2345 626Lacks 3`-OHAPH Resistant
    • Therapeutic AgentsKanamycinOOOOR1H2CHOHOR2H2NOHNH2HOH2CHONH2HO12345612346512345 6Kanosamine2-DeoxystreptamineKanamycin A: R1= NH2 ; R2 = OHKanamycin B: R1 = NH2 ; R2 = NH2Kanamycin C: R1= OH; R2 = NH2IIIIII Isolated from cultures of Streptomyces kanamyceticus. Theleast toxic member in the market is kanamycin A. It is used for the treatment of GI infections, such asdysentery and systemic G(-) bacillus infections caused byklebsiella, proteus, enterobacters. For disinfection of GI before an operation.
    • AmikacinOOOOH2NH2CHOHOOHH2NOHNH2HOH2CHONHHO12345612346512345 6AmikacinC COCH2 CH2 NH2OHH22-DeoxystreptamineKanosamine A semisynthetic derivative of kanamycin A. It is used in the treatment of infections causedby Mycobacterium tuberculosis, Yersiniatularensis, Pseudomona aeroginosa. The suffix “micin” denotes its origin.
    • TobramycinIsolated from cultures of Streptomycestenebrarius.Antimicrobial activity against resistanceP.aeroginosa.OOOOH2CNH2H2NOHNH2HONH2HO2-DeoxystreptamineTobramycinHOH2CHO1123451543 2345 626Lacks 3`-OHAPH Resistant
    • ParomomycinOOOOOOOHCH2OHH2NNH2HONH2HOHOOHHOHOR1R2 NH22-DeoxystreptamineD-GlucosamineParomomycin I: R1= H; R2= CH2NH2Paromomycin II: R1= CH2NH2; R2= HNeosamine B or C123345612345612344 512 Isolated from Streptomyces rimosus. In the tratment of GI infections caused byshigella, salmonella, E.coli, amoebas.
    • Spectinomycin An unusual aminoglycoside isolated from culturesof streptomyces spectabilis. The sugar portion has a carbonyl group and isfused through glycosidic bonds to the aminocyclitolportion, spectinamine. It is used in a single dose against Neisseriagonhorea.OOOCH3OH3CHNOHNHCH3 OHHOSpectinomycinSugarSpectinamine
    • NetilmicinOOHH3CNHCH3OHONHRHOOONH2CH2OHH2N1624 351234123545Sisomicin: R=HNetilmicin: R=C2H5 A semisynthetic ethyl derivative of sisomicin isolated fromMicromonospora inyoensis. Ethylation causes spacial hynderance against APH andATN enzymes. Against gentamicin resistant pseudomona and proteus.
    • Mechanism of Chemical incompatility ofAminoglycosides with β-lactams Acylation ofaminocyclitolportion by the β-lactam molecule. Begins withnucleophilicaddition of theamino group to thecarbonyl group ofβ-lactam ring.NONHCORHOOCONHCORHNHOOOSUGARNH2NSUGARHOOCH2NHOOOSUGARNH2SUGAR