Distamycin Analogues with Enhanced Lipophilicity:  Synthesis and Antimicrobial Activity

Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2004-04, Vol.47 (8), p.2133-2156
Main Authors: Khalaf, Abedawn I., Waigh, Roger D., Drummond, Allan J., Pringle, Breffni, McGroarty, Ian, Skellern, Graham G., Suckling, Colin J.
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Anti-Infective Agents - chemical synthesis
Anti-Infective Agents - chemistry
Anti-Infective Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal Agents - chemical synthesis
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
Biological and medical sciences
Cell Line
Cricetinae
Distamycins - chemical synthesis
Distamycins - chemistry
Distamycins - pharmacology
DNA - chemistry
Electrophoresis, Capillary
General aspects
Humans
Hydrophobic and Hydrophilic Interactions
Medical sciences
Microbial Sensitivity Tests
Pharmacology. Drug treatments
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocylic aminopropyl substituents. The ability of these compounds to bind principally to AT tracts of DNA has been evaluated using capillary zone electrophoresis. Significant antimicrobial activity against key organisms such as MRSA and Candida albicans is shown by several compounds, especially those containing a thiazole. Moreover, these compounds have low toxicity with respect to several mammalian cell lines.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm031089x