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QSAR studies on substituted 3- or 4-phenyl-1,8-naphthyridine derivatives as antimicrobial agents

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Abstract

Quantitative Structure Activity Relationship correlating the antitubercular and antibacterial (Staphylococcus aureus and Escherichia coli) activities with the structural descriptors of reported naphthyridine derivatives was developed. The data were divided into training and test sets. The former was used to develop the regression model and the latter was used to examine the predictive capability of these models. The statistical measures such as squared correlation coefficient (r 2 = 0.79–0.84), adjusted squared correlation coefficient (r 2 adj = 0.78–0.83) F-ratio (26.85–67.16), and cross-validation (q 2 = 0.74–0.79) were found to be satisfactory for all activities and the predictions were within the 99% confidence level. The models contained atom type, thermodynamic, structural, and electrotopological descriptors which emphasized the importance of the size, shape, and the lipophilicity of the molecule.

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Notes

  1. http://www.who.int/mediacentre/factsheets/fs104/en/ (7.1.08).

  2. http://graphics.med.yale.edu:5080/TriposBookshelf/sybyl/leapfrog/leapfrog_theory20.html1878 (2.1.08).

Abbreviations

QSAR:

quantitative structure activity relationship

WHO:

World Health Organization

SAR:

structure activity relationship

MTB:

M. tuberculosis

MDR-TB:

multi-drug resistant M. tuberculosis

MIC:

minimum inhibitory concentration

CVFF:

consistent valence force field

GFA:

genetic function approximation technique

LOF:

lack-of-fit

LMO:

leave more out method

SSE:

sum of squares of the error

TSS:

total sum of squares

PRESS:

predicted sum of squares

ADME:

absorption, distribution, metabolism, and excretion

Hf:

heat of formation

Jurs-PPSA-1:

sum of the solvent-accessible surface areas of all positively charged atoms

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Authors and Affiliations

  1. Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India

    Ponnurengam Malliappan Sivakumar, Geetha Iyer & Mukesh Doble

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  1. Ponnurengam Malliappan Sivakumar
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  2. Geetha Iyer
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  3. Mukesh Doble
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Correspondence to Mukesh Doble.

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Sivakumar, P.M., Iyer, G. & Doble, M. QSAR studies on substituted 3- or 4-phenyl-1,8-naphthyridine derivatives as antimicrobial agents. Med Chem Res 21, 788–795 (2012). https://doi.org/10.1007/s00044-011-9564-x

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