Cytotoxic urea Schiff base complexes for multidrug discovery as anticancer activity and low in vivo oral assessing toxicity

Abstract

Novel mononuclear complexes 2 – 8 derived from hybrid Urea Schiff base HL were synthesized using various metal Ni 2+ , Fe 3+ , Cu 2+ , Co 2+ , Mn 2+ , Zn 2+ , and Cr 3+ . The results revealed the ligand HL reacts with metal ions as monobasic or neutral monodentate chelator it via the nitrogen of azomethine and deprotonated/protonated phenolic oxygen atom adopting octahedral geometry. The elemental analysis of the complexes showed the bonding of the ligand with the metal ions in a ratio of 1: 1 in all-metal complexes. XRD analysis of the ligand and its complexes indicate a monoclinic, tetragonal, orthorhombic corresponding to urea Shiff base (1) and zinc complex ( 7), nickel complex ( 2) , and cobalt complexes ( 5), respectively. The bioactivity of synthesized compounds was tested and screened against three cancer cell lines PC3 (prostate), SK-OV-3 (ovarian), and HeLa (cervical). The results revealed a weak activity for the ligand, whereas nickel and iron complexes present moderate activities against three cancer cells. The best results were mentioned with copper and proved the best results against three cancer cells PC3 , SKOV3, and HeLa displaying an excellent activity with IC 50 values of 0.71 ± 0.06 , 0.12 ± 0.06, and 0.79 ± 0.23 μg/mL respectively. Moreover, the urea Schiff base complexes showed good safety in vivo toxicity test. The present study demonstrates that all urea Schiff base complexes is inactive against saint tissue and five metal complexes investigated herein can be effective and promising chemotherapeutic drugs for ovarian cancer cell SKOV3, emphasizing the copper-urea Schiff base complex.