Synthesis, Cytotoxicity Evaluation, DFT Molecular Modeling Studies and Quantitative Structure Activity Relationship of Novel 1,8-Naphthyridines

A series of substituted 1,8-naphthyridine derivatives were synthesized from 4-oxo-1,4-dihydro-1,8- naphthyridine-3-carbohydrazide (4) as starting material and investigated as cytotoxic and antitumor agents. Compound 4 reacted with different acid anhydrides to afford the corresponding imides and bis-imide derivatives 5-11. Pyridine and 1,8-naphthyridine derivatives 2-11 were tested for their in vitro cytotoxicity against four different cancer cell lines and structure activity relationship’s (SAR’s) was studied. Compounds 4-11 were studied theoretically using the density functional theory (DFT) with B3LYP/6-31(d) level of calculations, and the electronic properties of these compounds were related to their biological activity.