Exploring anticancer activity, acute toxicity, and molecular docking of synthesized schiff bases and schiff base-palladium complex

Herein, we present the synthesis and biological activity of novel Schiff bases, namely 2-(((2-((2-hydroxyethyl) amino)ethyl)imino)methyl)phenol (L1) and 4-bromo-2-(((2-((2-hydroxyethyl)amino)ethyl)imino)methyl)phenol (L2), along with the corresponding palladium complex of L1 [N-(2-hydroxyethylamino)ethylsalicylaldiminato]palladium(II) chloride] [Pd(L1)Cl]. Our study encompasses an evaluation of their acute toxicity and anticancer potential, as well as molecular docking simulations to elucidate their mechanisms of action. The compounds were characterized using various techniques, such as 1H NMR and 13C NMR. In addition, L2 was characterized using single-crystal X-ray diffraction (XRD). The toxicological results, along with biochemical and hematological analyses, revealed that a dose of 2 g/kg for L1 and 100 mg/kg for [Pd(L1)Cl] had no toxicological effects on mice. However, L2 displayed slightly higher toxicity, resulting in the death of a mouse at a dose of 2 g/kg, likely attributable to the presence of bromine. Notably, both the synthesized Schiff bases and the palladium complex exhibited cytotoxicity against four types of cancer cells: HT-1080, A-549, MCF-7, and MDA-MB-231 cell lines. Among them, the palladium complex demonstrated the most potent activity, with respective IC50 values of 13.24 & PLUSMN; 1.21, 25.24 & PLUSMN; 0.91, 38.14 & PLUSMN; 1.19, and 31.21 & PLUSMN; 2.56 & mu;M against HT-1080, A-549, MCF-7, and MDA-MB-231. Investigating the mechanism of action of the highly cytotoxic compound [Pd(L1)Cl], we found that it induced apoptosis by activating caspase-3/7 and caused G2/M-phase arrest while leading to the loss of mitochondrial membrane potential specifically in HT-1080 cells.