CoMFA study of distamycin analogs binding to the minor-groove of DNA: a unified model for broad-spectrum activity

Khedkar, Santosh A., Malde, Alpeshkumar K. and Coutinho, Evans C. (2007) CoMFA study of distamycin analogs binding to the minor-groove of DNA: a unified model for broad-spectrum activity. Journal of Molecular Modeling, 13 10: 1099-1108. doi:10.1007/s00894-007-0234-3


Author Khedkar, Santosh A.
Malde, Alpeshkumar K.
Coutinho, Evans C.
Title CoMFA study of distamycin analogs binding to the minor-groove of DNA: a unified model for broad-spectrum activity
Journal name Journal of Molecular Modeling   Check publisher's open access policy
ISSN 1610-2940
0948-5023
Publication date 2007-10-01
Sub-type Article (original research)
DOI 10.1007/s00894-007-0234-3
Volume 13
Issue 10
Start page 1099
End page 1108
Total pages 10
Place of publication Berlin
Publisher Springer-Verlag
Language eng
Subject 030404 Cheminformatics and Quantitative Structure-Activity Relationships
Abstract A 3D-QSAR analysis has been carried out by comparative molecular field analysis (CoMFA) on a series of distamycin analogs that bind to the DNA of drug-resistant bacterial strains MRSA, PRSP and VSEF. The structures of the molecules were derived from the X-ray structure of distamycin bound to DNA and were aligned using the Database alignment method in Sybyl. Statistically significant CoMFA models for each activity were generated. The CoMFA contours throw light on the structure activity relationship (SAR) and help to identify novel features that can be incorporated into the distamycin framework to improve the activity. Common contours have been gleaned from the three models to construct a unified model that explains the steric and electrostatic requirements for antimicrobial activity against the three resistant strains.
Keyword Broad-spectrum antibacterials
Distamycin analogs
DNA minor-groove binders
Drug-resistant bacterial strains (MRSA, VSEF, PRSP)
3D-QSAR
Unified CoMFA model
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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