1. Dreams of a “Magic Bullet”
Birth of Chemotherapy
Presentation was developed by Hugh Fackrell
Dreams of a “Magic Bullet”

2. Presentation Outline History “Sulfas” Ideal properties Sources
Salvorsan
Sulfa
Penicillin
“Sulfas”
Antimetabolites
antibiotic synergism
Ideal properties
Sources
Filename: Chemotheraphy.ppt

3. Semmelweiss Jena, Austria “Laying in” hospitals Peurperal fever
Cleanliness in surgery

4. Joseph Lister
Developed antiseptic surgery

5. Early Antibiotics Salvarsan 606- failure
Prontosil- developed by careful research
Penicillin- discovered accidently

6. Paul Ehrlich
Noble Prize
Chemotherapy
Theory of immunity

7. Salvarsan 606 Paul Ehrlich early 1900’s syphilis
arsenic + organic compound
Aniline dyes -
wasn't able to find the "magic bullet”

8. Prontosil 1930's, Gerhard Domagk 1935, Jacques and Therese Trefoncel
discovered that the active compound in Prontosil was Sulfanilamide
sulfanilamide “ Sulfas”

9. Sulfa Drugs

10. Sulfa vs PABA
Sulfanilamide
NH2
NH2SO2
PABA
NH2
HOOC

11. Effectiveness of Sulfas
Organism must synthesis folic acid
eg E coli
no effect if folic acid is required
eg man and many microbes
BACTERIOSTATIC

12. Structure of Sulfa Drugs
Sulfanilamide
Sulfisoxazole
Prontosil

13. Folic Acid Metabolism PABA + pteridine Dihydrofolic Acid
Pteridine synthetase
Dihydropteroic acid
[GTP]
Sulfonamide
Dihydrofolic Acid
Dihydrofolate Synthetase
L- Glutamine
Tetrahydrofolic Acid
Dihydrofolate synthetase
2 NADPH
2 NADP+
Trimethoprim
Thymidine
DNA
Purines
DNA, RNA
Methionine
tRNa, Proteins

14. Folic Acid Inhibition PABA + pteridine Dihydrofolic Acid
Sulfonamide
Dihydropteroic acid
Dihydrofolic Acid
Trimethoprim
Tetrahydrofolic Acid
Thymidine
DNA
Purines
DNA, RNA
Methionine
tRNa, Proteins

15. Antibiotic Synergism
Sulfisoxazole
Trimethoprim

16. Antibiotic Synergism Sulfonamide + trimethoprim
Effective dosage 10% of two separately
Broader spectrum of action
Reduce emergence of resistant strains

17. Alexander Flemming
Discovered penicillin

18. Penicillin 1928, Alexander Fleming 1938, Howard Florey and Ernst Chain
antibacterial activity in Penicillium mold (called it Penicillin)
1938, Howard Florey and Ernst Chain
developed Penicillin as an effective antibiotic

19. Inhibition of Staphylococcus by Penicillium
Staphylococcus Colony
Inhibition
Penicillium mould

20. Penicillin prevents Assembly of Bacterial Cell Walls

21. Penicillium Growing in Broth

22. Mass Production Used Many Flasks

23. Penicillium in Vats

24. Antimicrobial Therapy
Antimicrobics
substances produced by microbes that inhibit other microbes
Semi-synthetic antibiotics
naturally produced but altered
Synthetic antibiotics:
derived from chemicals

25. Ideal Properties of an Antibiotic
Low toxicity for patient
kills the invading microorganism without damaging the host
no adverse side reactions
non allergenic
High toxicity for microbe
bactericidal not bacteriostatic
broad spectrum
Low risk of other infections

26. More Characteristics
drug can be administered orally or parenterally (by injection)
Soluble in tissue fluids
absorbed by and dissolved in tissues or body fluids
levels of active drug sustained long enough to kill the invading agent
Long “Shelf” life

27. Still More Characteristics
Low probability of resistance
Microbial drug resistance develops slowly
microbicidal rather than microbistatic
Not inactivated by organic material
Assists the host in eliminating the infecting microbe
Not a powerful allergen

28. Sources of Antibiotics
Most spore-forming microorganisms
Fungi
Penicillium penicillin,
Cephalosporium griseofulvin
Bacteria
Bacillus bacitracin, polymyxin, tyrothricin, colimycin, gramicidin
Streptomycetes Aminoglycosides, chloramphenicol, erythromycin, tetracylcine, nystatin...