Linked Life Data

17107805

Source:http://linkedlifedata.com/resource/pubmed/id/17107805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-12-15
pubmed:abstractText
Structural optimization of the previously identified 4-(adamantan-1-yl)-2-quinolinecarbohydrazide (AQCH, MIC=6.25 microg/mL, 99% inhibition, Mycobacterium tuberculosis H37Rv) has led to two series of 4-(adamantan-1-yl)-2-substituted quinolines (Series 1-2). All new derivatives were evaluated in vitro for antimycobacterial activities against drug-sensitive M. tuberculosis H37Rv strain. Several 4-adamantan-1-yl-quinoline-2-carboxylic acid N'-alkylhydrazides (Series 1) described herein showed promising inhibitory activity. In particular, analogs 7, 9, 20, and 21 displayed MIC of 3.125 microg/mL. Further investigation of AQCH by its reaction with various aliphatic, aromatic, and heteroaromatic aldehydes led to the synthesis of 4-adamantan-1-yl-quinoline-2-carboxylic acid alkylidene hydrazides (Series 2). Analogs 42-44 and 48 have produced promising antimycobacterial activities (99% inhibition) at 3.125 microg/mL against drug-sensitive M. tuberculosis H37Rv strain. The most potent analog 35 of the series produced 99% inhibition at 1.00 microg/mL against drug-sensitive strain, and MIC of 3.125 microg/mL against isoniazid-resistant TB strain. To understand the relationship between structure and activity, a 3D-QSAR analysis has been carried out by three methods-comparative molecular field analysis (CoMFA), CoMFA with inclusion of a hydropathy field (HINT), and comparative molecular similarity indices analysis (CoMSIA). Several statistically significant CoMFA, CoMFA with HINT, and CoMSIA models were generated. Prediction of the activity of a test set of molecules was the best for the CoMFA model generated with database alignment. Based on the CoMFA contours, we have tried to explain the structure-activity relationships of the compounds reported herein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
626-40
pubmed:meshHeading
pubmed-meshheading:17107805-Adamantane, pubmed-meshheading:17107805-Antitubercular Agents, pubmed-meshheading:17107805-Chromatography, Thin Layer, pubmed-meshheading:17107805-Computer Simulation, pubmed-meshheading:17107805-Isoniazid, pubmed-meshheading:17107805-Least-Squares Analysis, pubmed-meshheading:17107805-Ligands, pubmed-meshheading:17107805-Magnetic Resonance Spectroscopy, pubmed-meshheading:17107805-Mass Spectrometry, pubmed-meshheading:17107805-Microbial Sensitivity Tests, pubmed-meshheading:17107805-Models, Molecular, pubmed-meshheading:17107805-Mycobacterium tuberculosis, pubmed-meshheading:17107805-Quantitative Structure-Activity Relationship, pubmed-meshheading:17107805-Quinolines, pubmed-meshheading:17107805-Rifampin, pubmed-meshheading:17107805-Spectrometry, Mass, Electrospray Ionization
pubmed:year
2007
pubmed:articleTitle
Synthesis, anti-tuberculosis activity, and 3D-QSAR study of 4-(adamantan-1-yl)-2-substituted quinolines.
pubmed:affiliation
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't