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

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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.

A unified CoMFA model for broad-spectrum DNA minor-groove binders

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Acknowledgements

SAK and AKM thank the Council of Scientific and Industrial Research (CSIR), India for the Fellowship. The computational facilities at BCP were provided by the All India Council for Technical Education (AICTE), India (F. No. 8022/RID/NPROJ/RPS-5/2003-04).

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  1. Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400 098, India

    Santosh A. Khedkar, Alpeshkumar K. Malde & Evans C. Coutinho

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  1. Santosh A. Khedkar
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  2. Alpeshkumar K. Malde
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  3. Evans C. Coutinho
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Correspondence to Evans C. Coutinho.

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Khedkar, S.A., Malde, A.K. & Coutinho, E.C. CoMFA study of distamycin analogs binding to the minor-groove of DNA: a unified model for broad-spectrum activity. J Mol Model 13, 1099–1108 (2007). https://doi.org/10.1007/s00894-007-0234-3

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  • DOI: https://doi.org/10.1007/s00894-007-0234-3

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