Abstract
Fifteen symmetrical 1,2-phenylenediamine Schiff’s base derivatives were designed as DNA intercalators. Adsorption, distribution, metabolism, elimination, and toxicity (ADMET) properties and drug-likeliness of the designed compounds were predicted by Swiss-ADME software, and the molecular docking study was performed in the PyRx tool. Four Compounds NHM01, NHM04, NHM06 and NMH11 were synthesized and the structure of each compound was analyzed using Fourier transform infrared spectroscopy (FTIR), 1H NMRand13C NMR. Moreover, the four compounds were in vitro biologically screened for their interactions with the genomic DNA. The binding properties of these compounds to genomic DNA (G-DNA) were investigated by UV-visible absorption and fluorescence spectroscopy. The molecular docking studies of compounds revealed that all the compounds are bioactive, however, compound NHM01 shows significant DNA binding affinity over standard drugs. The biological results indicate that the four synthesized compounds can interact with G-DNA by intercalation binding. Compound NHM01 showed the highest key selection vector (KSV) value, followed by NHM04, which suggests that compound NHM01 binds most tightly to G-DNA. Our results demonstrate that NHM01 and NHM04may serve as novel lead compounds for the discovery of more 1,2-phenylenediamine Schiff’s base derivatives with improved anticancer potency and selectivity.