Binding of vinca alkaloid analogues to human serum albumin and to alpha 1-acid glycoprotein.
The binding of a series of vinca alkaloid analogues having eburnane or indolo[2,3-a]quinolizidine skeletons was studied with human serum albumin (HSA) by affinity chromatography and with alpha 1-acid glycoprotein by means of competition experiments. On HSA the binding occurs at the benzodiazepine-indole binding site via hydrophobic interaction and shows slight stereoselectivity preferring the trans isomers. The binding to alpha 1-AGP proved to be highly stereoselective in favour of the trans isomers having 3(S),16(R)eburnane or 1(R),12b(S)indolo[2,3-a]quinolizidine absolute configurations.
Fitos
I
I
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Visy
J
J
Simonyi
M
M
D001665:Binding Sites; D001667:Binding, Competitive; D002846:Chromatography, Affinity; D004952:Esters / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D009961:Orosomucoid / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014748:Vinca Alkaloids / Q000378:metabolism* / Q000493:pharmacokinetics
D004952:Esters; D007211:Indoles; D009961:Orosomucoid; D012709:Serum Albumin; D014748:Vinca Alkaloids; C032858:apovincaminic acid; C013983:vinpocetine