Syntheses, biological evaluation and QSAR study on antitumor activity of 1,5-N,N′-disubstituted-2-(substituted benzenesulphonyl) glutamamides

Article abstract of DOI:10.1016/S0968-0896(02)00007-X

We have reported [unpublished data] the synthesis and QSAR of 5-substituted-2-(substituted benzenesulphonyl) glutamines which have shown the importance of steric factor on the aliphatic chain. N-Phthalyl isoglutamine, having the substitution at position 1 of the glutamic acid moiety, is the metabolite of recently approved thalidomide for different types of tumors by US FDA. Based on these, 36 new 1,5-N,N′-disubstituted-2-(substituted benzenesulphonyl) glutamamides were synthesized, as tools for further elucidation of the structural requirements for antitumor activity. All the synthesized compounds were tested for antitumor activity against Ehrlich Ascites Carcinoma (EAC) in Swiss albino mice using tumor weight as inhibitory parameter. Quantitative structure-activity relationship (QSAR) studies of these analogues revealed that the electron donating groups on the phenyl ring are found to be mandatory for the activity which was also proved by the negative coefficient of indicator parameter I_3, for NO₂ group on the phenyl ring. Molecular volume (MV) and steric factor at R₅ position also plays a role in ligand-receptor interactions.