Anticancer Compounds Based on Isatin-Derivatives: Strategies to Ameliorate Selectivity and Efficiency.

In this review we compare and discuss results of compounds already reported as anticancer agents based on isatin-derivatives, metalated as well as non-metallated. Isatin compounds can be obtained from plants, marine animals, and is also found in human fluids as a metabolite of amino acids. Its derivatives include imines, hydrazones, thiosemicarbazones, among others, already focused on numerous anticancer studies. Some of them have entered in pre-clinical and clinical tests as antiangiogenic compounds or inhibitors of crucial proteins. As free ligands or coordinated to metal ions, such isatin derivatives showed promising antiproliferative properties against different cancer cells, targeting different biomolecules or organelles. Binding to metal ions usually improves its biological properties, indicating a modulation by the metal and by the ligand in a synergistic process. They also reveal diverse mechanisms of action, being able of binding DNA, generating reactive species that cause oxidative damage, and inhibiting selected proteins. Strategies used to improve the efficiency and selectivity of these compounds comprise structural modification of the ligands, metalation with different ions, syntheses of mononuclear and dinuclear species, and use of inserted or anchored compounds in selected drug delivery systems.

N,N',N'' versus N,N',O imine-containing coordination motifs: ligand-directed synthesis of mononuclear and binuclear CuII compounds.

It is demonstrated here that tridentate imine ligands can control the nuclearity of copper(II) complexes based on the donor atoms present in the ligand. The N,N',N''-donating imine ligand led to a mononuclear compound, namely di-chlorido-[N,N-dimethyl-N'-(pyridin-2-yl-methyl-idene)ethane-1,2-di-amine]copper(II) monohydrate, [CuCl2(C10H15N3)]·H2O, 1, while the N,N',O-donating imine ligand produced a binuclear metal complex, namely µ2-chlorido-di-chlorido-(µ2-2-{[2-(di-methyl-amino)-ethyl]imino-methyl}phenolato)(N,N-dimethyl-ethylene-di-amine)-dicopper(II) 0.11-hydrate, [Cu2(C11H15N2O)Cl3(C4H12N2)]·0.11H2O, 2. The structure of 2 is a remarkable example of a binuclear copper(II) complex containing a single substituted 2-imino-methyl-phenolate ligand that has two copper(II) sites in square-pyramidal coordination.

Synthesis and crystal structure of di-chlorido-(1,10-phenanthroline-κ2N,N')gold(III) hexa-fluorido-phosphate.

A gold(III) salt of composition [AuCl2(C12H8N2)]PF6 was prepared and characterized by elemental and mass spectrometric analysis (ESI(+)-QTOF-MS), 1H nuclear magnetic resonance measurements and by single-crystal X-ray diffraction. The square-planar coordination sphere of AuIII comprises the bidentate 1,10-phenanthroline ligand and two chloride ions, with the AuIII ion only slightly shifted from the least-squares plane of the ligating atoms (r.m.s. = 0.018 Å). In contrast to two other previously reported AuIII-phenantroline structures that are stabilized by inter-actions involving the chlorido ligands, the packing of the title compound does not present these features. Instead, the hexa-fluorido-phosphate counter-ion gives rise to anion⋯π inter-actions that are a crucial factor for the crystal packing.