Contributions of paul ehrlich

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1. “Founder of Chemotherapy” Paul Ehrlich Presented by: Dr. Pratibha Tiwari 2. Nobel Prize of Physiology and Medicine 1908 Founder of Modern Chemotherapy…
  • 1. “Founder of Chemotherapy” Paul Ehrlich Presented by: Dr. Pratibha Tiwari
  • 2. Nobel Prize of Physiology and Medicine 1908 Founder of Modern Chemotherapy Contribution in the field of: Histology, Haematology, Immunology, Oncology, Microbiology and Pharmacology
  • 3. • Standardization of manufacturing of Anti-Diphtheria serum • Discovery of Salvarsan (arsphenamine): First Magic Bullet • Synthesis of anti-bacterials • Concept of chemoreceptor and chemotherapy • Concept of concept of linking chemical structure of compounds to their pharmacological activities • Concept of developing resistance
  • 4. Staining Procedures... He concluded that strong affinities must exist between biological structures and the stain applied.  Studied entire spectrum of staining techniques and chemistry involved  Differential staining of tissues using Methylene Blue  First detect bilirubin in urine of the patients of Jaundice ( Diazo reaction)  Stained and named “Mast cells” using alkaline dyes  Differentiated Leukocytes into Basophils, Eosinophils and Neutrophils  First showed nucleated RBCs and subdivided into Megaloblast, Microblast, Normoblast and Poikiloblast  Methylene blue also stained the long appendages of nerve cells  Developed a new staining procedure for Mycobacterium which later became basis of current Zielh-Neelsen Acid- fact staining
  • 5. Serum research... • Formulated “Side-chain Theory” proposing a possible explanation for the process of immunity. • Gave concept of acquired immunity and mechanism of transfer of immunity from mother to foetus. • Alongwith Emil Behring work on Standardization of Anti-Diptheria serum production process : “Valency of serums” Side-chain Theory • Introduced the term “Receptor”, developed the theory of chemoreceptor. • A side-chain from a given cell might have a molecular structure that allowed it to bind with a specific toxin or bacteria leading to its loss of action. • This leads to trigger production of more such side-chains and secreted in the blood. This way small amount of toxin of toxin can produce a large amount of anti-toxin. • Ehrlich later argued that certain chemoreceptors on parasites, microorganisms, and cancer cells would be different from analogous structures in host tissues, and that these differences could be exploited therapeutically
  • 6. Chemotherapy: • In vivo staining • Methylene blue as anti-malarial agent • Transition from Experimental pharmacology to Therapeutic pharmacology • The search for a “Chemotherapia specifica” : concept of Structure– Activity Relationship • Development of first synthetic chemotherapeutic agent: From Atoxyl to Salvarsan and Neosalvarsan against syphilis Cancer research: • Achieved insight that when tumors are cultivated by transplanting tumor cells, their malignancy increases from generation. • If primary tumor is removed, then metastasis precipitously increases.
  • 7. Paul Ehrlich’s Magic Bullets: If a compound could be made that selectively targeted a disease-causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. • Need to study the relationship between the chemical composition of drugs and their mode of action in the organisms • Selective drugs were needed which, like anti-toxins aimed specifically at their corresponding toxins • High parasitotropism with low organotropism
  • 9.  In 1858, David Livingston suggested use of 1% aqueous solution of potassium arsenite(Fowler’s reagent) for the treatment of sleeping sickness  1859- first synthesised ‘Atoxyl’ (Aminophenyl arsenic acid) by Pierre Jaceus Antoine Be’champ  Paul Ehrlich and Alfred Bertheim first derived structure of Atoxyl  Atoxyl : high doses for prolonged period were required(2% patients get optic nerve atrophy) in use till 1905.  Acetylatoxyl (arsacetin): less toxic but high doses needed ; damage to vestibular nerve  Arsenoxides and Arsenobenzenes (reduced products; metabolites)  Arsenophenyl glycine: effective against sleeping sickness, low toxicity,also effective against spirochetes or syphillis; 1907  Arsenophenol
  • 10.  Arsphenamine or Salvarsan (Ehrlich and Hata; 1909 against syphillis):30% arsenic, treatment 18 months long with 20 arsphenamine injestions and 30-40 bismuth injections; difficult to prepare on large scale  Neoarsphenamine or neosalvarsan: sodium bisulphite aldehyde derivative; 19 % arsenic, less toxic , short treatment time, easily oxidised  In 1930 Mapharsen (oxophenarsine, metabolite of arsphenamine) very stable.  Melarsobol or Arsobal, injectable arsenic derivative remains in use as the treatment of choice for sleeping sickness.
  • 11. Atoxyl (arsernic acid anilide) Atoxyl (Aminophenyl arsenic acid) Acetylatoxyl Arsacetin Spirasyl (arsenophenylglycine) Arsenophenol Arsphenamine (diaminodioxyarsenobenzol) Salvarsan Neoarsphenamine Neosalvarsan Oxophenarsine Mapharsen Melarsoprol Arsobal Trimers and Pentamers Of arsphenamine (Salvarsan main constituents)
  • 12. Development of Sufanilamides
  • 13. Sulfa drugs or Sulfanilamides • First synthetic chemotherapeutic agent effective against bacterial disease. • Gerhard Domagk(1932) hypothesized that since the dye worked by binding to the proteins in fabric and leather, it might also bind to the proteins in bacteria , thus inhibiting their action • In 1936, Prontosil or sulfamidochrysoidine, a dye, was successfully used against puerperal sepsis, also effective against meningitis , pneumonia, and streptococcal infections, childbed fever, blood poisoning, gonorrhea, burns from gas warfare, and other serious burns • Most effective sulfa drugs were sulfapyridine for pneumonia, sulfathiazole against pneumonia and staphylococcus, sulfaguanadine to treat dysentery , and sulfadiazine, which worked against pneumonia, strep and staph. Prontosil
  • 14. Prontosil
  • 15. SAR of sulphanilamides
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