1,5-N,N'-Disubstituted-2-(Substituted Benzenesulphonyl)- Glutamamide Analogues as Anticancer Agents. Part 3. † Synthesis, Biological Screening and QSAR Study #
BioChem Press, Shovanlal Gayen, Bikash Debnath, Soma Samanta, Balaram Ghosh, Anindya Basu, Tarun Jha · 2005
Motivation. 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. Method. 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. Results. The final QSAR model obtained has correlation coefficient, standard error of estimate and cross– validated R 2 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. Conclusions. 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.