DNA-binding affinities and sequence specificities of protoberberine alkaloids and their demethylated derivatives: a comparative study.
Berberrubine (1a), jatrorubine (2a), and palmatrubine (3a) have been chemically prepared by partial demethylation of berberine (1), jatrorrhizine (2), and palmatine (3), respectively. Their interactions with calf thymus (CT) DNA, poly(dA-dT)poly(dA-dT), poly(dG-dC)poly(dG-dC), and eight AT-rich 12-mer double-stranded DNAs have been investigated by means of competitive ethidium bromide (EB) displacement experiments. The results showed that DNA-binding affinities of these protoberberine alkaloids have been significantly improved by partial demethylation, and that all of these alkaloids have the preferable binding affinities with AT-rich DNA. Especially, the sequence specificities of DNA-binding of demethylated derivatives 1a, 2a, and 3a had changed to a certain extent when compared with the parent alkaloids 1, 2, and 3, respectively. The binding mode of these alkaloids was further confirmed by UV spectroscopic titration experiments. All the compounds bind to double-stranded DNA most probably via an intercalating mode.
Qin
Yong
Y
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
Chen
Wen-Hua
WH
Pang
Ji-Yan
JY
Zhao
Zhong-Zhen
ZZ
Liu
Liang
L
Jiang
Zhi-Hong
ZH
D001483:Base Sequence; D001600:Berberine Alkaloids / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D003640:Dealkylation; D004365:Drugs, Chinese Herbal / Q000032:analysis; D004996:Ethidium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet
D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; C009090:protoberberine; D004247:DNA; D004996:Ethidium