Linked Life Data

21426935

Source:http://linkedlifedata.com/resource/pubmed/id/21426935

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2011-5-9
pubmed:abstractText
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a central transcription factor that regulates the anti-oxidant defense system and is considered as a modifier for several inflammatory diseases. Thus, activation of Nrf2 provides pivotal therapeutic target for developing therapy against these diseases. Herein, a chemo-enzymatic methodology is designed and developed to make PEGylated curcumins as water soluble drug candidates with enhanced aqueous solubility and bioavailability. For this, curcumin was judiciously converted to diester (1) using ethyl ?-bromoacetate and potassium carbonate. The diester 1 in subsequent step was copolymerized with poly(ethylene glycol) using Candida antarctica lipase [CAL-B, Novozym 435] under solventless condition. C. antarctica selectively does trans-esterification and only catalyses reaction of the primary hydroxyls of poly(ethylene glycol). It does not affect the secondary enolic hydroxyls of curcumin, thus leaving behind the active group unaltered. A luciferase based reporter gene assay was used for primary screening for identifying a novel Nrf2 activator. Most of the PEGylated curcumin analogs strongly activate Nrf2 several folds higher than the free curcumin but copolymer 3a was identified as the most potent Nrf2 activator. Copolymer 3a induces Nrf2-driven NQO1 expression in a concentration dependent manner. Furthermore, a plausible mechanism for quantitative structure-activity relationship is also discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1879-0720
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16-24
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Design, synthesis and evaluation of novel PEGylated curcumin analogs as potent Nrf2 activators in human bronchial epithelial cells.
pubmed:affiliation
Institute of Nano-science and Engineering Technology, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA. mpandey1@partners.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural