Linked Life Data

7650681

Source:http://linkedlifedata.com/resource/pubmed/id/7650681

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1995-9-27
pubmed:abstractText
Echinocandin B (ECB) is a lipopeptide composed of a complex cyclic peptide acylated at the N-terminus by linoleic acid. Enzymatic deacylation of ECB provided the peptide "nucleus" as a biologically inactive substrate from which novel ECB analogs were generated by chemical reacylation at the N-terminus. Varying the acyl group revealed that the structure and physical properties of the side chain, particularly its geometry and lipophilicity, played a pivotal role in determining the antifungal potency properties of the analog. Using CLOGP values to describe and compare the lipophilicities of the side chain fragments, it was shown that values of > 3.5 were required for expression of antifungal activity. Secondly, a linearly rigid geometry of the side chain was the most effective shape in enhancing the antifungal potency. Using these parameters as a guide, a variety of novel ECB analogs were synthesized which included arylacyl groups that incorporated biphenyl, terphenyl, tetraphenyl, and arylethynyl groups. Generally the glucan synthase inhibition by these analogs correlated well with in vitro and in vivo activities and was likewise influenced by the structure of the side chain. These structural variations resulted in enhancement of antifungal activity in both in vitro and in vivo assays. Some of these analogs, including LY303366 (14a), were effective by the oral route of administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
3271-81
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Semisynthetic chemical modification of the antifungal lipopeptide echinocandin B (ECB): structure-activity studies of the lipophilic and geometric parameters of polyarylated acyl analogs of ECB.
pubmed:affiliation
Natural Products Research Division, Lilly Research Laboratories, Eli Lilly and Company Inc., Indianapolis, Indiana 46285, USA.
pubmed:publicationType
Journal Article