dendrimers bind antioxidant polyphenols and cisplatin drug树枝状分子结合抗氧化多酚和顺铂药物.pdfVIP

Dendrimers Bind Antioxidant Polyphenols and cisPlatin Drug 1 1 1 2 Amine Abderrezak , Philippe Bourassa , Jean-Sebastian Mandeville , Reza Sedaghat-Herati , Heidar-Ali Tajmir-Riahi1* ´ ´ ´ ` ` ` ´ 1 Departement de Chimie-Biologie, Universite du Quebec a Trois-Rivieres, Trois-Rivieres, Quebec, Canada, 2 Department of Chemistry, Missouri State University, Springfield, Missouri, United States of America Abstract Synthetic polymers of a specific shape and size play major role in drug delivery systems. Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with potential applications in gene and drug delivery. We examine the interaction of several dendrimers of different compositions mPEG-PAMAM (G3), mPEG-PAMAM (G4) and PAMAM (G4) with hydrophilic and hydrophobic drugs cisplatin, resveratrol, genistein and curcumin at physiological conditions. FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyse drug binding mode, the binding constant and the effects of drug complexation on dendrimer stability and conformation. Structural analysis showed that cisplatin binds dendrimers in hydrophilic mode via Pt cation and polymer terminal NH2 groups, while curcumin, genistein and resveratrol are located mainly in the cavities binding through both hydrophobic and hydrophilic contacts. The overall binding constants of durg-dendrimers are ranging from 102 M21 to 103 M21. The affinity of dendrimer binding was PAMAM-G4.mPEG-PAMAM-G4.mPEG-PAMAM-G3, while the order of drug-polymer stability was curcumin.cisplatin.genistein.resveratrol. Molecular