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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. June 2005, Volume 4, Number 6, 393-412 |
QSAR Study on 5-N-Substituted-2-(Substituted Benzenesulphonyl)
Glutamines as Antitumor Agents through Synthesis and Biological Evaluation: Part III
Bikash Debnath, Soma Samanta, Shovanlal Gayen, Anindya Basu, Balaram Ghosh, and Tarun Jha
Internet Electron. J. Mol. Des. 2005, 4, 393-412
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Abstract:
The importance of the non-essential amino acid, glutamine, to the
proliferation of human tumour cells was well established. It is one
of the two major, if not the only, substrate of cancer. It helps in
tumor cell growth by supplying its amide nitrogen atom in the
biosynthesis of other amino acids, purine, and pyrimidine bases.
Tumor is a "nitrogen trap" as well as "glutamine trap". Hence, the
efforts were made to synthesize series of glutamine analogs,
evaluate these biologically and QSAR study was performed to
explore the substitutional requirements essential for improved
anticancer activity. QSAR study was performed using Log of
percentage tumor weight inhibition as dependent parameter and
physicochemical parameter, ETSA indices and indicator variable
as independent parameters through multiple linear regression
analysis. Some of the compounds showed promising anticancer
activity. This study resulted some QSAR models with 86.49,
83.61, 88.52, 88.41 and 88.00% of explained variances. All these
models showed more than 80% predicted variance. QSAR study
revealed that aliphatic substitution of the glutamine analogs might
have played an important role in the hydrophobic/dispersive
interaction with the possible glutamine receptor. This study also
showed that field effect at R1 position
and resonance effect at R2
position might increase anticancer activity. Some of the atoms of
the general structure were identified as pharmacophore. At least
one free hydrogen in amide moiety of glutamine analogs might be
essential for the anticancer activity. This study throws some light
in the structural requirements essential for improved anticancer
activity and will help to find out substituents for future synthesis of
this type of analogs.
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