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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. October 2002, Volume 1, Number 10, 488-502 |
1,5-N,N-Disubstituted-2-(Substituted Benzenesulphonyl)-Glutamamides
as Antitumor Agents. Part 2. Synthesis, Biological Activity and QSAR Study
Bikash Debnath, Kolluru Srikanth, Suchandra Banarjee, and Tarun Jha
Internet Electron. J. Mol. Des. 2002, 1, 488-502
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Abstract:
Cancer has been described as a nitrogen trap. Tumor cells are avid
glutamine consumers. Glutamine (GLN), which is a glutamic acid
derivative, supplies its amide nitrogen to tumor cells in the
biosynthesis of purine and pyrimidine bases. Isoglutamines, which
have 1-N-amide instead of 5-N-amide and 5-COOH instead of
1-COOH in glutamine, showed antitumor activities. Thus,
compounds containing both 1- and 5-amido group (i.e.
glutamamide) may have potential antitumor activity. In
continuation of our complex program for the development of new
potential anticancer agents through rational drug design, 28 new
1,5-N,N-disubstituted-2-(3,4-disubstituted
benzenesulphonyl)-glutamamides were selected for synthesis, biological
evaluation and QSAR study. These compounds were synthesized and
screened against Ehrlich Ascites Carcinoma (EAC) cells in Swiss
Albino mice. A QSAR study was performed in order to design
leads with increased effectiveness for antitumor activity using the
Hansch approach. Some of the synthesized compounds showed
excellent yields and several of then were found to have good
antitumor activity. The QSAR study showed that low hydrophobic
or hydrophilic substitution at benzene ring, electron withdrawing
group at para and electron donating group at meta position
of benzene ring and less bulky alkyl substitution at aliphatic side
chain may result in appreciable antitumor activity. This study
throws some light in the future design of this type of compounds
with better anticancer activity.
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