Carbonyl side-chain of catechol compounds is a key structure for the suppression of copper-associated oxidative DNA damage in vitro.
Catechol is possibly carcinogenic to humans (International Agency for Research on Cancer, IARC). The key mechanism could include its oxidative DNA-damaging effect in combination with reductive-oxidative metals like Cu. We found that DNA damage was suppressed by introducing an α-carbonyl group to catechol at C4-position to produce carbonyl catechols. During the oxidative DNA-damaging process, catechols but not carbonyl catechols were oxidized to o-quinone; however, coexisting Cu(II) was reduced to Cu(I). Carbonyl catechols were possibly arrested at the oxidation step of semiquinones in the presence of Cu(II). Cu(I)-binding to DNA was stronger than Cu(II)-binding, on the basis of the circular dichroism spectral change. None of the carbonyl catechols induced such change, suggesting sequestration of Cu(I) from DNA. Solid-phase extraction experiments and spectrophotometric analyses showed the formation of semiquinone chelates with Cu(I). Thus, chelate formation could explain the suppression mechanism of the Cu-catechol-dependent DNA damage by terminating the reduction-oxidation cycle. Structural modifications such as introducing an α-carbonyl group to catechol at C4-position would contribute to reducing the risk and improving industrial and medical potentials of aromatic/phenolic compounds sustaining our daily lives.
Ando
Motozumi
M
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
Nishida
Hiroyuki
H
Nishino
Yoshihiko
Y
Ohbayashi
Manabu
M
Ueda
Koji
K
Okamoto
Yoshinori
Y
Kojima
Nakao
N
D002396:Catechols / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D003300:Copper / Q000633:toxicity*; D004249:DNA Damage; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
D002396:Catechols; D003300:Copper; C034221:catechol