title: [Design, synthesis and anti-oxidative evaluation of L-amino acid prodrugs of scutellarein].
abstract: To design and synthesize a series of novel scutellarein 4'-L-amino acid prodrugs with more potent anti-oxidative activity and improved physicochemical properties. Scutellarein was used as lead compound, according to successful experience of improving bioavailability of oral administration drugs by active transport mechanism, principle of hybridization was used to introducing L-amino acid structural fragments at 4'-position of scutellarein to design and synthesize target scutellarein 4'-L-amino acid prodrugs. The synthetic compounds were tested on their physicochemical properties and in vitro anti-oxidative activity against H202 induced oxidative damage in PC12 cells. Five compounds were found to have more potent anti-oxidative activity than positive control VE. Moreover the physicochemical properties of synthesized compounds were evaluated, and the results revealed that L-amino acid ether derivatives are more stable (t1/2 9-92 h) than their corresponding ester derivatives (t1/2 0.5 h). Water solubility of scutellarein 4'-L-amino acid ester and ether derivatives were 1 796-4 100 microg.mL-1 and 27.7-81.1 microg.mL-1 respectively, in comparison with scutellarin, the solubility of compounds 18, 19 and 22, 24-27 increased about 120-280 fold and 2-6 fold respectively. All these results suggested that L-amino acid prodrug strategy has significant potential in scutellarein prodrug design.
authors.affiliation: School of Pharmacy, Guiyang Medical College, Guiyang 550004, China.
authors.forename: Xiao-zhong
authors.initials: XZ
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yong-lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Yan-yu
authors.initials: YY
authors.lastname: Lan
authors.forename: Ai-min
authors.initials: AM
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Feng-jing
authors.initials: FJ
authors.lastname: Xing
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D047310:Apigenin / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D015195:Drug Design; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016716:PC12 Cells; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D011355:Prodrugs; D047310:Apigenin; D007770:L-Lactate Dehydrogenase; C458179:scutellarein