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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. September 2007, Volume 6, Number 9, 280-301 |
QSAR for Analogs of 1,5-N,N'-Disubstituted-2-(substituted benzenesulphonyl)
Glutamamides as Antitumor Agents
Parthasarathi Panda, Soma Samanta, Sk. Mahasin Alam, Soumya Basu, and Tarun Jha
Internet Electron. J. Mol. Des. 2007, 6, 280-301
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Abstract:
Cancer is a widespread and life threatening disease for which new and
improved drugs are needed. It is well established that the
transformation of the normal cells to a cancerous phenotype is often
associated with cognate changes in the transport and metabolism of
nutrients such as glucose and glutamine. Many tumor cells are
particularly avid glutamine consumers. Glutamine also plays a key role
in tumor cell energetics, and several tumor cell lines use glutamine as
their major respiratory fuel. Based on our composite program of
development of new potential anticancer agents through rational
design, 32 analogs of 1,5-N,N'-disubstituted-2-(substituted
benzenesulphonyl) glutamamide were synthesized, characterized and
biologically evaluated against Ehrlich Ascites Carcinoma (EAC) cells
in Swiss Albino mice. Tumor cell inhibition was considered as the
biological activity parameter. A QSAR study was performed on this
data set, showing the importance of ETSA and RTSA indices of
several atoms, the energy of HOMO, the energy gap between HOMO
and LUMO, as well as the approximate surface area. The QSAR study
highlights the atomic features and molecular descriptors that determine
the antitumor activity of these glutamamides analogs. These
computational models also illustrate the importance of atomic charge,
energy of HOMO, and energy of LUMO for the biological activity.
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