Nucleic Acids in Chemistry and Biology

Covalent Interactions of Nucleic Acids with Small Molecules and Their Repair 305

NHAc N

Ac

OH NOC 6 H 11 O 6

Ac

NHAc N

Ac

OSO 3 N

Ac

OAc

HO

NAc

NAc

NAc

N

N

N N

dR

NH 2

O

H

NH

Ac

N

N

HN

N

dR

HN

O

S

N

Me

NH 2

R

S

N

Me

NH

F NH 3 Cl

ONH 3 Cl

CYP450

10%

inactive glucuronate

CYP450

90%

inactive 3-, 5-, 7- and9-hydroxy metabolites

i ii

proximate carcinogen

iii

nitrenium intermediate

two identified products

from DNA binding

4

DF 203 (NSC 674495); R = H5F 203 (NSC 703786); R = F Phortress (NSC 71305)

b

a

Figure 8.14 (a) Metabolic activation of 2-acetylaminofluorene (AAF) and its binding to dG via a hypothetical
nitrenium intermediate. (b) Examples of benzothiazolyl anticancer agents. Processes: (i) sulfotransferase;
(ii) acetyl transferase; and (iii) binding to DNA in vitro or in vivo

NH 2

R NR" 2

N

NO 2

O

R

NHAc

N

N

NHR

Me 2 NNMe 2

NH

2-naphthylamine

R = R' = H; 4-aminobiphenyl

R = H, R' = O; 4-nitrobiphenyl

R=NH 2 , R' = H; benzidine

4-nitroquinolineN-oxide

2-acetylaminofluorene R = H; 4-aminoazobenzene

R = Me; 4-methylaminoazobenzene

auramine

Figure 8.13 Examples of N-aryl carcinogens