*11.7.5. Methylation*

*11.7.3. Epoxide hydration*

492 Drug Discovery

oxizane ring as shown below:

*11.7.4. Acetylation*

drazides (figure 10)

R1 R2

CH CH

Drug substrate - epoxide

The glucuronide conjugates can be excreted via the bile or urine.

O

Acetate + CoA CH3

SH

H

N

crobial agent sulfanilamide which is secreted from the body.

N-

N- acetylsulfanilamide

acetyl

transferase

C

O

CH3

A number of aromatic compounds are transformed by phase I reactions to form epoxide intermediates. The epoxides are reactive electrophilic species that can bind covalently to proteins and nucleic acids to bring about toxic effects. These epoxides are detoxified via the nucleophilic attack of water molecule on one of the electron deficient carbon atoms of the

+ H <sup>H</sup><sup>+</sup>

Acetylation is achieved by cytosolic enzymes known as N-acetyl transferases which catalyze transfer of acetate from acetyl co-enzyme A to primary aromatic amine or hy‐

Acetyl CoA

C

S

O

SO2 NH2

**Figure 10.** Acetylation reations leading to the formation of N– Acetylsulfanilamide, the final metabolite of the antimi‐

OH

epoxide hydrolase R1

CH

OH

CoA

Sulfanilamide

H2N SO2 NH2

CH

OH

R2

Most of the methyl transferases are cytosolic enzymes. They utilize S-adenosyl methionine (SAM) as the methyl donor. The final metabolite, thiopurine, has antineoplastic properties and is used as an anticancer agent (Figure 11)

**Figure 11.** Methylation reactions leading to the formation of methylthiopurine
