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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. August 2005, Volume 4, Number 8, 556-578 |
1,5-N,N'-Disubstituted-2-(Substituted Benzenesulphonyl)-Glutamamide Analogues
as Anticancer Agents. Part 3. Synthesis, Biological Screening and QSAR Study
Shovanlal Gayen, Bikash Debnath, Soma Samanta, Balaram Ghosh, Anindya Basu, and Tarun Jha
Internet Electron. J. Mol. Des. 2005, 4, 556-578
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Abstract:
Numerous studies on glutamine metabolism in cancer demonstrate
that glutamic acid and glutamine analogues may be developed as
possible antitumor agents. Efforts were made to synthesize
glutamamide analogues, structural variants of glutamic acid and
glutamine, contains both the amido groups at 1 and 5 positions of
glutamic acid and derivatives of both glutamine and isoglutamine.
Twenty eight new 1,5-N,N'-disubstituted-2-(substituted
benzenesulphonyl) glutamamides were synthesized in continuation
to our earlier work. These compounds were screened for antitumor
activity and a QSAR study was performed to explore the
substitutional requirements for the improved anticancer activity
using physicochemical and topological parameters. The final
QSAR model obtained has correlation coefficient, standard error of
estimate and cross-validated R2 of 0.889, 0.068 and 0.697,
respectively. This QSAR study showed the importance of
particular atoms and identified a functional region of the molecule
with the potential as the pharmacophore related with
dispersive/van der Waals and electronic interaction with the
receptor(s). The study also showed that the increased molar
volumes of these analogues have advantageous effect to the
antitumor activity. The study helps to understand the relationship
of the chemical structure of this type of compounds with the
anticancer activity. The QSAR study may be helpful for further
synthesis of highly active glutamamide analogues as antitumor
agents.
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