Pharmaceutical

Sciences X

Medicinal Chemistry and

Pharmacology of Antimicrobial
Drugs
 Classification
Cell Wall synthesis inhibitors • Penicillin's, Cephalosporin's, Vancomycin

Protein Synthesis inhibitors • Aminoglycosides, Macrolides, Tetracycline’s, Lincosamide

DNA Synthesis inhibitors • Quinolones/Fluoroquinolones, Metronidazole

Folate Inhibitors • Sulfonamides, Trimethoprin

R = Substitution of R effects in solubility's salts are
given orally:
R = benzyl penicillin = Pen G.
R = Phenoxymethy = Pen V
 Drug-Drug
Incompatibility

A chemical drug-drug
incompatibility between
gentamycin C2a and beta lactam.
Two drugs react with each other
so that N-acylation of C1 of
gentamycin by the beta lactam
bond takes place, thus inactivates
both antibiotics.
 Erythromycin, clarithromycin and
azithromycin

Macrolides
Mechanism: Protein synthesis inhibitors.

Structure: Large lactones ring of 12 or

14 or 16 atoms are attached to amino
sugar (hexose) & neutral sugar by
glycosidic link.
Macrolide…

They are contraindicated in

hepatic failure.
 Erythromycin

• Lactone ring + desoamine (amino

sugar) + cladinose (neutral sugar).
Erythromycin
• Common SEs. Gastric upset is due to Erythromycin and
conversion of erythromycin to ketal. tetracycline cross placenta
in appreciable amounts
QT prolongation. and also appear in breast
• The macrolides are generally unstable milk.
to acids, bases & high temperature.
 • Stable to acids, bases & high temp, thus less gastric
upset.
Azithromycin • Long half life, greater and longer tissue penetration
and covers H. influenza.

• The enhanced lipophilic allows for lower or less

Clarithromycin frequent doses.
 CYP3A4 INH
ERYTRHOMYCIN †††↓†††↓†††↓
CLARITHROMYCIN ††††††↓†††↓†
††↓
AZITHROMYCIN †††††↓†††↓††
†
 Tetracycline's

Tetracycline, Doxycycline and

Minocycline
 • Tetracycline a-stereo orientation of the C4 dimethylamino-
moiety is essential for the bioactivity.
• Epitetracycline is inactive drug by epimerization.

Chemical
instability
 Tetracycline with C7 chlorine, absorb light in
the visible region leading to free radical
generation and potentially cause severe
erythema to sensitive patient on exposure to
sunlight.
Photo
Toxicity
 Comparison…

Tetracycline Doxycycline Minocycline

Less SEs. Less SEs High SEs. Has reactive amino acid. Causes serum
Hepatitis, liver necrosis from iv, sickness (discoloration of nail, bones, teeth).
avoid in pregnancy. Vestibular toxicity (vertigo, ataxia, nausea), dizzy,
Pediatric (<8y) tooth headache
discoloration.
Empty stomach With or after food but With/without
empty better absorbed
Renal safe
Effective acne Effective acne More effective for acne due to lipid soluble.
Used in RA.
Dis with bi, tri valent Less Dis. More Less DI
photosensitive
Once daily, bioavail 90-100%
Expired tetracycline cause Funconi like
syndrome (renal tubular necrosis,
diabetes like symptoms) and extreme
cases has been fatal.
 Quinolones & Fluoroquinolones

Nalidixic acid (urinary disinfectant)

Fluoroquinolones 1st gen. Nalidixic acid, Norfloxacin
2nd gen. Ciprofloxacin, Oflaxacin
3rd gen. Gatifloxacin, Moxifloxacin, Levofloxacin (respiratory
tract)
4th gen Travofloxacin, basifloxacin
  Inhibition of DNA gyrase (topoisomerase
II) and topoisomerase IV makes cell
inaccessible and leads to cell death.
Quinolones &  Different quinolones inhibit different
Fluoroquinolones extent of topoisomerase II and IV.
 DNA gyrase seems more important in
gram –ve.
MOA  Topoisomerase IV in gram +ve.
 Nalidixic acid is primary effective against
gram –ve.
 Nalidixic acid is
primary effective
against gram –ve.

Quinolones chelate with polyvalent

ions such as Fe, Al, Mg, Ca to form
less water-soluble and complexes
and thus decrease considerable
potency.
Nitrofurantoin
• Nitrofurontoin inhibits bacterial
DNA and RNA.
• Not used in renal diseases or
contraindicated in CrCl <60 ml/min
• The drug of choice in urinary tract
infection and also used as
prophylaxis for UTI in pregnancy
100 mg BID for 7 days.

Rapid GI absorption & high urinary

concentration
Folate antagonist sulfa drugs
(Cotrimoxazole):

DNA
Thymidine

Tetrahydrofolic
acid

Dihydroteroic
acid

Dihydroteroate
diphosphate + PABA
 • Mechanism:
Binds to bacterial ribosomes to inhibit
protein synthesis.
• Side effects:
Oxazolidinones: Reversible thrombocytopenia.
Linezolid (po, • Drug interactions:
parenteral). It can cause serotonin syndrome with
antidepressants.
• Therapeutic use:
Methicillin resistant S. aureus (MRSA)
infections