Fujita Ban Analysis of Some Substituted Glutamamides

Abstract

Introduction: Like glucose, glutamine is a major substrate for the cancer cell. Glutamine supplies the major portions of nitrogen atoms in the synthesis of DNA and RNA. Numerous studies on glutamine metabolism in cancer show that glutamic acid and glutamine analogs may be developed as future anticancer agents. A QSAR study was performed on some previously synthesized glutamine analogs to understand the substitutional requirements for their anticancer activity. Twenty-eight 1,5-N, N’-disubstituted-2-(substituted benzenesulphonyl) glutamamides were considered and the QSAR study was performed using the Fujita-Ban model, which does not require the use of physico-chemical parameters. A software Tanagra v1.4 was used to calculate the contribution of substituents to biological activity by PLSR analysis. A good QSAR model was obtained considering the biological activity of 25 analogs (3 compounds were not considered as they gave a poor r² value of 0.66) as evidenced by the statistical data (r=0.823, s=0.049067). The study helps to understand the relationship of the chemical structure of the glutamine analogs with the anticancer activity in a lucid manner and may be helpful in the synthesis of future glutamine analogs with better biological activity.