Metallo - Bioactive Compounds as Potential Novel Anticancer Therapy

Abstract

Mono and bi-organometallic complexes of Cu(II), Ni(II), Mn(II), Zn(II) and Ag(I) complexes with oxaloamide ligand has much potential as therapeutic and diagnostic agents. The ligand allows the thermodynamic and kinetic reactivity of the metal ion to be controlled and also provide a scaffold for functionalization. Specific examples involving the design of metal complexes as anticancer agents are discussed. These complexes have been synthesized and characterized by (1H-NMR, mass, IR, UV-VIS, ESR) spectra, magnetic moments and conductance measurements, elemental and thermal analyses. Molar conductances in DMF solution indicates that, the complexes are non-electrolytes. The ESR spectra of solid Cu(II) complexes (2-5) show an axial type indicating a d(X2-y2) ground state with a significant covalent bond character. However, Mn(II) complex(9), shows an isotropic type indicating an octahedral geometry. Cytotoxic evolution IC50 of the ligand and its complexes have been carried out. Cu(II) Complexes show enhanced activity in comparison to the parent ligand or standard drug. Copper is enriched in various human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However, the use of copper binding ligand to target tumor, copper could provide a novel strategy for cancer selective treatment. the indicate the of water molecules, thermal analyses (DTA and were carried out to certain their nature. The thermal curves in the temperature 27-600°range for complexes ( 2 ), ( 3 ), ( 4 ), ( 5 ) and ( 6 are thermally stable up to 45 °C. Broken of hydrogen bonding occurs as endothermic peak within the temperature 45-50 °C as shown in (Table Dehydration is characterized by endothermic peak at the temperature 85 °C, corresponding to the loss of hydrated water molecules as in complex ( 5 ). The elimination of coordinated water molecules occur in 130-150°C range accompanied by endothermic peaks as in complexes ( 2 ), ( 3 ), ( 4 ), ( 5 ) and ( 6 ) [60,61]. The TG and DTA thermogramof Cu(II) complex ( 2 ) showed that, the complexes decomposed in five steps. The first occurred at 50°C with no weight loss as endothermic peak, may be due to break of hydrogen bonding. The second step occurred at 150°C with 5.50% weight loss (Calc. 5.65%) could be due to the elimination of two coordinated H 2 O. The TG curve displays another thermal decomposition at 265°C with 9.99% weight loss (Calc. 10.16%), which could be due to the loss of acetate group. The complex shows an exothermic peak observed at 320°C is due its melting point. Finally, exothermic peaks appear at 455, 504, 559, 580 and 595 °C corresponding to oxidative thermal decomposition which proceeds slowly with leaving CuO with 14.71% weight loss (Calc. 14.75%) 62 . The TG and DTA thermogramof Cu(II) Complex ( 5 ) shows endothermic peak at 85 °C, with 5.03% weight loss (Calc. 5.07%) due to The biological activity of the ligand (1) and its metal complexes (2) , (3) , (4) , (5) , (9) and (10) were evaluated against HEPG-2 cell line.In this study, we try to know the chemotherapeutic activity of the tested complexes by comparing them with the standard drug (Vinblastine Sulfate). The treatment of the different complexes in DMSO showed similar effect in the tumoral cell line used as it was previously reported[63]. The solvent dimethyl sulphoxide (DMSO) shows no effect in cell growth. The ligand (1) shows a weak inhibition effect at ranges of concentrations used, however, the complexes showed better effect against HEPG-2 cell line. The obtained data indicate the surviving fraction ratio against HEPG-2 tumor cell line increasing with the decrease of the concentration in the range of the tested concentrations. Also, the Cu(II) complex (2) shows the highest potency of inhibition at 500 µg/ml against HEPG-2 cell line, compared with the standard drug [51].Cytotoxicity results indicated that the tested complexes (2)