General Principles of Chemotherapy - Strategies to develop Chemotherapeutic drugs

THis Presentation gives a clear idea about the targets in microorganisms (MO) to selectively inhibit MO without causing a major damage to human cells to develop chemotherapeutic agents.

1. General Principles of Chemotherapy BY Dr. Ramanachary Namoju M.S, PhD

2. Chemotherapy - Basics Invader = foreign organism entering to human body internal invaders = cancer cells external invaders = Infectious agents Infectious agent = Microbe or parasite ( helmenths ) Pathogen Commensal Prion 1 st antimicrobial agent is Arsenial compound, Salvarsan Developed for Syphillis by Ehrlich

3. General Principles of Chemotherapy Treatment of invaders using chemicals is called as Chemotherapy Basic principles are Biochemical difference b/w host and infectious organism Selectivity and sensitivity Treatment vs Prophylaxis

4. Targets for Antibacterial Chemotherapy Class I Reactions (synthesis of building blocks) Class II Reactions (synthesis of micro molecules) Class III Reactions (synthesis of macro molecules) Formed cell structures

5. Drugs targeting Class-I reactions These are not used as targets as there are no differences b/w host and invader in Class –I reactions EMF pathway (Glycolysis) TCA cycle So as of now, there is no drug that target the Class-I reactions.

6. Drugs targeting Class-II reactions Folate metabolism Sulfonamides Trimithoprim Proguanil Pyrimithamine

7. Drugs targeting Class-III reactions Peptidoglycan layer synthesis inhibitors Protein Synthesis inhibitors DNA/RNA Synthesis inhibitors

8. Drugs targeting Formed Cell Structures Drugs act on Cell membrane Polymixins (bacteria) Polyene Abs ( Nystatin , Amphotericin - in bacteria) Drugs act on DNA Bleomycin – DNA fragmenter Acridines - Intercalating agents Mytomycin – Covalent Binder Drugs act on Microtubules Vincristin , vinblastin Albendazole Drugs act on Muscles Pyrantel Ivermectin Levimisole Piperazine

9. Drugs targeting Class-II reactions Folate Metabolism: Sulfonamides Trimithoprim Methotrexate Drug Bacteria Human Protozoa Trimethoprim + + Methotrexate + + Proguanil Pyrimethamine + +

10. Drugs targeting Class-III reactions Cell Wall (Peptidoglycan) layer Synthesis

11. Inside = cytoplasm Outside = exoplasm Plasma Membrane NAM U P P L- Alanine D- Alanine Alanine Recimase D-Ala-D-Ala Ligase C55 Lipid P NAM U P P U P P NAG P U P NAM C55 Lipid P P NAM U P P NAG

12. Inside = cytoplasm Outside = exoplasm Plasma Membrane C55 Lipid P P NAM NAG C55 Lipid P P NAM NAG

13. Inside = cytoplasm Outside = exoplasm Plasma Membrane C55 Lipid P P 1 2 3 4 NAG NAM 1 2 3 4 NAM 1 2 3 4 NAG NAM 1 2 3 4 NAG NAM

14. NAM UDP L- Alanine D- Alanine Alanine Recimase D-Ala-D-Ala Ligase + NAM UDP C55 Lipid P UMP C55 Lipid P P NAM NAG UDP NAG UDP C55 Lipid P P C55 Lipid P P P NAM NAG NAM NAG NAM NAG NAM NAG NAM NAG NAM NAG Vancomycin Fospomycin Cycloserine Bacitracin Beta - Lactams Transpeptidation Mura-A Translocase Mura-Y Tunicamycin