Fundamentals of Medicinal Chemistry

Table 7.2 Examples of drugs that inhibit the formation of cell wall synthesis

Compound/Active against Structure Mode of action

D-Cycloserine. A broad spectrum

antibiotic.

N

H

O C O

H

H

H

NH 3

D-Cycloserine

O

H C O

H

H

H

NH 3

D-Alanine

Inhibits the enzymes alanine racemase and

D-alanyl-D-alanyl synthetase that are

responsible for producing the dipeptide

D-alanyl-D-alanine, a precursor of the

pentapeptide chain in cell wall formation. It

is believed that the rigid structure of the

isoxazole ring gives the drug a better chance

of binding to the enzyme than the more

flexible structure of D-alanine.

Fosomycin. Active against Gram-positive

and Gram-negative bacteria.

O

H 3 C

H H

O

P

O−

O−

Fosomycin

Inhibits enol-pyruvate transferase, which

catalyses the incorporation of

phosphoenolpyruvic acid (PEP) into uridine

diphospho-N-acetylglucoamine

(UDPNAG), a precursor involved in the

formation of bacterial cell walls.

Bacitracin A. Active against Gram-positive

bacteria. The configurations of the amino

acid residues are given in the brackets.

Believed to inhibit a number of the stages in

the biosynthesis of the peptidoglycan

chains. (Letter key, see Table 1.1.)

Bacitracin A

L

(L)

E

(D)

I

(L)

K

(L)

D

(L)

CH 3

CH 3

NH 2

N

S

OC

N

H (D)

(L)

F

(D)

Orn

(D)

I

(L)

b-Lactam group of antibiotics. More

effective against Gram-positive than Gram-

negative bacteria but some cephalosporins,

such as ceftazidime, are very effective

against Gram-negative bacteria.

Theb-lactam group of antibiotics inhibit

cell wall synthesis by inhibiting the

formation of the transpeptidases responsible

for the cross linking between the

peptidoglycan chains.

N

O

RCONH

H H

S

X

COOH

Penicillins

Cephalosporins

R−

R− X−

Benzylpenicillin

(Penicillin G)

Ampicillin (X = H)

Amoxicillin (X = OH)

CH 2

NH 2

X

(D)

Cephalothin

Ceftazidime

S CH^2

−CH 2 N

HOOCC(CH 3 ) 2 O

N

S

H 2 N

N

−OCOCH 3

S

N

O

RCONH

H H

CH 3

CH 3

HCOOH

EXAMPLES OF DRUGS THAT DISRUPT CELL MEMBRANES AND WALLS 137