Towards the Development of Anticancer Drugs from Andrographolide: Semisynthesis, Bioevaluation, QSAR Analysis and Pharmacokinetic Studies
2015
Isolation of andrographolide from Andrographis paniculata , preparation of a library of derivatives
via 1,3-dipolar cycloaddition of andrographolide with azomethine ylides generated from isatin
derivatives or acenaphthoquinone and seconday α-amino acids, evaluation of the anticancer potential
of the products, quantitative structure activity relationship studies and pharmacokinetic parameter
determination have been described. 2D QSAR studies revaled that steric effects and van der Waals interactions
play major roles in the determination of antiproliferative activity of these derivatives. 3D QSAR study predicted
that the benzyl substitution at N 20 position may be important for higher steric interaction. Pharmacokinetic studies with
two most potent analogues revealed moderate chemical stability but poor aqueous solubility, metabolic stability and permeability
with significant CYP3A4 inhibition.
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