Substituent effect on the chemical and biological properties of diisatin dihydrazone Schiff bases: DFT and docking studies

Abstract

According to the considered role of lipophilicity-hydrophobicity on organic Schiff base hydrazones, different substituents of phenyl, ethyl, and methyl groups were inserted in the synthetic strategy of diisatin dihydrazones (L1–4). The biochemical enhancement was evaluated depending on their inhibitive potential of the growth power of three human tumor cells, fungi, and bacteria. The biochemical assays assigned the effected role of different substituents of phenyl, ethyl, and methyl groups on the effectiveness of their diisatin dihydrazone reagents. The interacting modes with calf thymus DNA (i.e. Ct-DNA) were studied via viscometric and spectrophotometric titration.

The organo-reagent L1 with the oxalic derivative assigned a performed inhibitive action for the examined microbes and the human tumor cell lines growing up over the terephthalic (L4) > malonic (L2) > succinic (L3) ones. From K_b = binding constant, and $∆G_b^{\ne }$ = Gibb’s free energy values, the binding of interaction within Ct-DNA was evaluated for all compounds (L1–4), in which L1, L3, and L4 assigned the highest reactivity referring to the covalent/non-covalent modes of interaction, as given for (L1–4), 14.32, 13.28, 10.87, and 12.41 × 10⁷ mol⁻¹ dm³, and −45^.17, −43.24, −43.75, and −44.05 kJ mol⁻¹, respectively. DFT and docking studies were achieved to support the current work.