Amplification of DNA-binding affinities of protoberberine alkaloids by appended polyamines.
This communication describes a synthetic approach toward the amplification of the moderate DNA-binding affinities of protoberberine alkaloids. Specifically, three protoberberine derivatives bearing two to six primary amino groups at the 3- and 9-positions of protoberberine were synthesized and characterized by NMR ((1)H and (13)C) and HRMS. Studies on their affinities toward calf thymus (CT) DNA by ethidium bromide (EB) displacement and spectrophotometric titration experiments indicate that these polyamino protoberberines show more than 10(3)-fold enhanced DNA-binding affinities relative to palmatine and thus are exploitable as strong DNA-binders.
Pang
Ji-Yan
JY
School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, PR China.
Long
Yu-Hua
YH
Chen
Wen-Hua
WH
Jiang
Zhi-Hong
ZH
D000215:Acylation; D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001600:Berberine Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D004247:DNA / Q000187:drug effects*; D004996:Ethidium; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000737:chemistry
D000470:Alkaloids; D001600:Berberine Alkaloids; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D011073:Polyamines; C009090:protoberberine; D004247:DNA; D004996:Ethidium