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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. August 2003, Volume 2, Number 8, 539-545 |
QSAR Study on Some Substituted Glutamine Analogs as Anticancer Agents
Tarun Jha, Bikash Debnath, Soma Samanta, and Arun Uday De
Internet Electron. J. Mol. Des. 2003, 2, 539-545
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Abstract:
After glucose, glutamine is a major substrate for the cancer cell.
In the synthesis of DNA and RNA, major portions of nitrogen
atoms are supplied by glutamine (GLN). Structural variants of
glutamine may antagonize enzymes involved in DNA and RNA
synthesis. A QSAR (quantitative structure-activity relationships)
study was performed on some previously synthesized glutamine
analogs in order to get insight in the substitutional requirements
for their anticancer activity as well as to overcome the symmetry
restriction of De Novo model and time consuming determination
of partition coefficients of Hansch analysis. The QSAR study
was performed using the Fujita Ban model. A good QSAR model
was obtained considering anticancer activity, i.e., log % of tumor
weight inhibition which expresses the biological activity, of
thirty 5-N-substituted-2-(substituted
benzenesulphonyl)-L-glutamines as dependent
variable and substitutional contribution
at specific position as independent variable as evidenced by the
statistical data (r = 0.8122, s = 0.1196, F = 1.3755). Substituent
at the 3' and 5'- positions of the phenyl ring lead to a general
decreased anticancer activity, but a Br at the 4'-position and a Cl
at the 2'-position were positively correlated to the total activity.
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