Linked Life Data

16884306

Source:http://linkedlifedata.com/resource/pubmed/id/16884306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2006-8-3
pubmed:abstractText
On the basis of suggestions derived either from a pharmacophoric model for antitubercular agents or from a structure-activity relationship analysis of many pyrroles previously described by us, we report here the design and synthesis of new analogues of 1,5-(4-chlorophenyl)-2-methyl-3-(4-methylpiperazin-1-yl)methyl-1H-pyrrole (BM212). Various substituents with different substitution patterns were added to both positions 1 and 5 of the pyrrole nucleus to evaluate their influence on the activity toward Mycobacterium tuberculosis (MTB) and atypical mycobacteria. Biological data showed that, although some nontuberculosis mycobacterial strains were found to be sensitive, MIC values were higher than those found toward MTB. The best compound (1-(4-fluorophenyl)-2-methyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole, 5) possessed a MIC of 0.4 microg/mL (better than BM212 and streptomycin) and a very high protection index (160), better than BM212, isoniazid, and streptomycin (6, 128, and 128, respectively). Finally, molecular modeling studies were performed to rationalize the activity of the new compounds in terms of both superposition onto a pharmacophoric model for antitubercular compounds and their hydrophobic character.
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
10
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4946-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Antimycobacterial agents. Novel diarylpyrrole derivatives of BM212 endowed with high activity toward Mycobacterium tuberculosis and low cytotoxicity.
pubmed:affiliation
Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università La Sapienza, P. le A. Moro 5, 00185 Rome, Italy. mariangela.biava@uniroma1.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't