Exploring the structure-activity relationship (SAR) of Schiff bases as effective compounds in scavenging free radicals

Naphthol-imine compounds containing N-phenylethylenediamine ( 1 ) and quinoline amine ( 2 ) moieties were synthesized and characterized. Density Functional Theory (DFT) calculations were performed aiming to obtain information on the chemical properties of these molecules. In silico ADME/Tox profile analyses were performed on molecules 1 and 2 using the web tools pkCSM-pharmacokinetics, Molinspiration, and Osiris Property Explorer. Drug -likeness levels of 1 and 2 were predicted according to the Lipinski rules. The radical scavenger activity of compounds 1 and 2 was determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH . ) and 2,2 ' -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS . + ). Molecules 1 and 2 were ineffective as radical scavengers in the DPPH radical capture assay at the test doses. However, 1 showed activity in eliminating ABTS + radical with IC 50 = 17.4 +/- 0.9 mu M. The neutral red assay determined the cytotoxicity of 1 and 2 against the V79 cell line. Molecule 1 was more cytotoxic than 2 , with IC 50 values of 36.67 mu M and 51.26 mu M, respectively. The alkaline comet assay was used to investigate the in vitro genotoxicity of 1 and 2 . After 24 h of exposure to a dose of 20 mu M, 1 did not cause significant DNA damage compared to non -exposed cells. The compounds were tested for toxicity using Artemia saline assay.