Linked Life Data

7915437

Source:http://linkedlifedata.com/resource/pubmed/id/7915437

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1994-9-26
pubmed:abstractText
Systemic side effects of antiinflammatory steroids may be minimized by incorporation of a metabolically labile group which is metabolized to make the steroid inactive upon entry into the systemic circulation (antedrug concept). In continuing efforts to minimize systemic adverse effects of potent antiinflammatory steroids, we have recently synthesized methyl 11 beta, 17 alpha, 21-trihydroxy-3,20-dioxopregna-1,4-diene-6-carboxylate (P6CM), its 21-acetoxys (P6CMa, P6CMb) and 17,21-acetonide (P6CMacet) derivatives. Structure-activity relationships have now been assessed and compared with prednisolone (P) for glucocorticoid receptor affinity (P IC50 = 28 nM), gluconeogenic activity as induction of tyrosine aminotransferase (EC50 = 4.4 nM) in H4-II-C3 HTC cells and antiproliferative effects (P = 48% inhibition of [3H]thymidine incorporation at 1 microM). Relative potencies for receptor binding (P = 1) were 0.12, 0.03, 0.004, and 0.0008 for P6CM, P6CMa, P6CMb, and P6CMacet, respectively, and enzyme induction relative potencies were 0.13, 0.05, 0.01, and 0.008, respectively. Antiproliferative effects of all derivatives were also less than that of P. These decreases suggest that addition of the 6-carboxymethyl group to prednisolone results in the general reduction of glucocorticoid activities. Taken together with previously reported results demonstrating retention of topical antiinflammatory activity of these novel steroids, P6CM and its derivatives may represent new locally active antiinflammatory steroids with reduced propensity to cause gluconeogenic and antiproliferative adverse effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0039-128X
pubmed:author
pubmed:issnType
Print
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
324-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Receptor binding affinity and antiproliferative activity of new antiinflammatory antedrugs: 6-methoxycarbonyl prednisolone and its derivatives.
pubmed:affiliation
Florida A & M University, College of Pharmacy and Pharmaceutical Science, Tallahassee 32307.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.