Antibiotics-Inhibitors of nucleic acid biosynthesis

Antibiotics - Mode of action involve the inhibition of nucleic acid biosynthesis

1. Antibiotics – Inhibitors of nucleic acid biosynthesis Applied Microbiology (BTN-514) Submitted by Sourik Dey (18610023), M.Sc Biotechnology, 1 st Year, 2018-2019 Submitted to Dr Vikas Pruthi

2. Inhibitors of nucleic acid biosynthesis Quinolones:- Norfloxacin , Nalidixic acid , Ciprofloxacin. Inhibit bacterial topoisomerases and DNA gyrases. Rifamycins:- Rifampin. Inhibit bacterial RNA-polymerase.

3. Inhibitors of DNA Synthesis Selectivity due to differences between prokaryotic and eukaryotic enzymes

4. QUINOLONES The quinolones are really not antibiotics. By definition, an antibiotic means something that’s produced by another living substance. That’s the real definition. We have a lot of chemotherapeutic antimicrobials that have activity against organisms for which we loosely use the term antibiotic, but they are really chemicals.

5. CHEMISTRY OF QUINOLONES www.antibioticdirectory.com

6. MECHANISM OF ACTION They block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication. Inhibition of topoisomerase IV probably interferes with separation of replicated chromosomal D NA into the respective daughter cells during cell division.

7. • Mode of action - These antimicrobials bind to the A subunit of DNA gyrase (topoisomerase) and prevent supercoiling of DNA, thereby inhibiting DNA synthesis . • Spectrum of activity - Gram-positive cocci and urinary tract infections. • Resistance - Common for Nalidixic acid ; developing for ciprofloxacin. Quinolones (bactericidal) Nalidixic acid , ciprofloxacin, ofloxacin , norfloxacin, levofloxacin, lomefloxacin, sparfloxacin

8. Inhibitors of RNA Synthesis Selectivity due to differences between prokaryotic and eukaryotic RNA polymerase

9. RIFAMYCIN B STRUCTURE www.antibioticdirectory.com

10. MECHANISM OF ACTION Inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase. Halts initiation of mRNA transcription. Prevention of translation of polypeptides.

11. • Mode of action -These antimicrobials bind to DNA-dependent RNA polymerase and inhibit initiation of mRNA synthesis . • Spectrum of activity -Wide spectrum but is used most commonly in the treatment of tuberculosis. • Resistance -Common. • Combination therapy -Since resistance is common, rifampin is usually used in combination therapy. Rifampin, Rifamycin, Rifampicin, Rifabutin ( bactericidal)