Structural analysis of catechin derivatives as mammalian DNA polymerase inhibitors.
The inhibitory activities against DNA polymerases (pols) of catechin derivatives (i.e., flavan-3-ols) such as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin, (+)-catechin gallate, (-)-epicatechin gallate, (-)-gallocatechin gallate, and (-)-epigallocatechin gallate (EGCg) were investigated. Among the eight catechins, some catechins inhibited mammalian pols, with EGCg being the strongest inhibitor of pol alpha and lambda with IC(50) values of 5.1 and 3.8 microM, respectively. EGCg did not influence the activities of plant (cauliflower) pol alpha and beta or prokaryotic pols, and further had no effect on the activities of DNA metabolic enzymes such as calf terminal deoxynucleotidyl transferase, T7 RNA polymerase, and bovine deoxyribonuclease I. EGCg-induced inhibition of pol alpha and lambda was competitive with respect to the DNA template-primer and non-competitive with respect to the dNTP (2'-deoxyribonucleotide 5'-triphosphate) substrate. Tea catechins also suppressed TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation, and the tendency of the pol inhibitory activity was the same as that of anti-inflammation. EGCg at 250 microg was the strongest suppressor of inflammation (65.6% inhibition) among the compounds tested. The relationship between the structure of tea catechins and the inhibition of mammalian pols and inflammation was discussed.
Mizushina
Yoshiyuki
Y
Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Hyogo, Japan. mizushin@nutr.kobegakuin.ac.jp
Saito
Akiko
A
Tanaka
Akira
A
Nakajima
Noriyuki
N
Kuriyama
Isoko
I
Takemura
Masaharu
M
Takeuchi
Toshifumi
T
Sugawara
Fumio
F
Yoshida
Hiromi
H
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry*; D003198:Computer Simulation; D004259:DNA-Directed DNA Polymerase / Q000032:analysis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000032:analysis / Q000737:chemistry; D006801:Humans; D008322:Mammals; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015203:Reproducibility of Results; D013045:Species Specificity; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D002392:Catechin; D004259:DNA-Directed DNA Polymerase